Disease-Modifying Effects of Non-Invasive Electroceuticals on β-Amyloid Plaques and Tau Tangles for Alzheimer’s Disease
Abstract
:1. Introduction
2. Electrical Fields
2.1. Transcranial Direct Current Stimulation (tDCS)
2.1.1. Tau Tangle
2.1.2. β-Amyloid Plaques
2.2. 40-Hz Gamma Oscillations Using Electrical Stimulation
Stimulation | Stimulation Intensity | Duration | Subject | Main Finding | Reference |
---|---|---|---|---|---|
tDCS stimulation | |||||
Active electrode: right forntal cortex Counter: vental thorax | +0.2 mA | 20 min 10 sessions in 2 weeks | Female Sprague Dawley rats Aβ injected in hippocampus | - ↑ density of nissl’s body in deeper hippocampus - ↑ ChAT level - no significant difference in the neurofibrillary tangles (NFT)-like changes - ↓ spatial learning and memory dysfunction | [17] |
Active electrode: anterior to lambda Counter: anterior to bregma | +0.05 mA | 20 min 15 sessions in 3 weeks | 3xTg AD | - Insignificant change in total tau, pTau and APP level - no effect in improving memory performance | [19] |
Active electrode: frontal cortex Counter: chest and abdomen | +0.15 mA | 30 min 10 sessions in 2 weeks | APP/PS1 C57 mouse | - ↑ NF200 level in hippocampus - ↓ Aβ42 level in hippocampus - ↓ GFAP level in hippocampus - ↑ spatial learning and memory in the early stage APP/PS1 transgenic mouse | [15] |
- ↓ Aβ42 level in hippocampus - ↓ GFAP level in hippocampus - ↑ spatial learning memory and recognition memory | [20] | ||||
- ↓ Aβ level in hippocampus and frontal cortex - ↓ level of Iba1 and GFAP in hippocampus and frontal cortex - ↑ ADAM 10, NeuN, LRP1 and PDGRFβ hippocampus and frontal cortex | [21] | ||||
Active electrode: left prefrontal cortex Counter: ventral thorax | +0.3 mA | 20 min 5 sessions in 5 days | APP/PS1 B6C3 mouse | - No significant effect on total Aβ concentrations in hippocampus - ↑ spatial learning, recognition and working memory | [16] |
−0.3 mA | |||||
40 Hz gamma oscillation | |||||
Flicking light and sound | - | 1 h 4 or 8 weeks | 10 MCI patients | - No significant changes in CSF Aβ and tau - ↑ functional connectivity between posterior cingulate cortex and precuneus - Downregulation of immune factors with engagement of the neuroimmune system - ↑ network functional connectivity after 8 weeks of daily flicker | [37] |
tACS Electrode: bilateral temporal lobes | 2 mA | 1 h 4 weeks | 4 AD patients | - ↓ significantly in pTau level in brain - No significant changes in level of Aβ and microglia activation - No significant changes in overall cognition | [42] |
taVNS bilateral auricular concha | 1.8 mA | 30 min 15 days | 14 APP/PS1 mice | - ↓ significantly in Aβ42 expression and soluble Aβ40 and Aβ42 levels in the hippocampus - ↓ P2X7R/NLRP3/caspase-1 pathway to regulate microglia pyroptosis - ↓ pro–IL-1β and pro–IL-18 to suppress inflammation - ↑ microglial phagocytosis - ↑ Spatial Learning and Memory | [47] |
3. Transcranial Magnetic Stimulation (TMS)
4. Electromagnetic Radiation
4.1. Electromagnetic Field Stimulation (EMFS)
4.2. Infrared Light Stimulation
4.3. Radiation Therapy
5. Transcranial Focused Ultrasound
5.1. Focused Ultrasound
5.1.1. Focused Ultrasound with Microbubbles Infusion (FUS-MB)
5.1.2. Focused Ultrasound with Microbubble Infusion and Drug Delivery
6. Conclusions and Perspectives
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
AD | Alzheimer’s disease |
MRI | Magnetic Resonance Imaging |
Aβ | Amyloid-β |
pTau | phosphorylated Tau |
BBB | Blood–Brain Barrier |
tDCS | transcranial Direct Current Stimulation |
TNF-α | Tumor Necrosis Factor alpha |
NFT | Neurofibrillary Tangle |
NF-κB | Nuclear factor κB |
EEG | Electroencephalogram |
MCI | Mild Cognitive Impairment |
APP | Amyloid Precursor Protein |
PS1 | Presenilin-1 |
GFAP | Glial Fibrillary Acidic Protein |
NF200 | Neurofilament 200 |
DG | Dentate Gyrus |
BACE1 | Beta-secretase 1 |
ADAM10 | Disintegrin and metalloproteinase domain-containing protein 10 |
CSF | Cerebrospinal Fluid |
tACS | transcranial Alternating Current Stimulation |
VNS | Vagus Nerve Stimulation |
LC | Locus Coeruleus |
TMS | Transcranial Magnetic Stimulation |
BK | Large conductance calcium-activated potassium |
GSK-3β | Glycogen Synthase Kinase 3β |
ApoE | Apolipoprotein E |
PP2A | Protein Phosphatase 2A |
LC3 | Microtubule-associated protein light chain 3 |
PI3K | Phosphatidylinositol 3-Kinase |
Akt | protein kinase B |
EMF | Electromagnetic Field |
EMP | Electromagnetic Pulse |
PHB | Primary Human Brain |
SAR | Specific Absorption Rate |
HSP | Heat Shock Protein |
IR | Ionizing Radiation |
LDIR | Low-Dose Ionizing Radiation |
HDIR | High-Doses of Ionizing Radiation |
JNK | c-Jun N-terminal Kinase |
MAPK | p38 Mitogen-Activated Protein Kinase |
MRgFUS | MRI-guided Focused Ultrasound |
LIFU | Low-Intensity Focused Ultrasound |
PRF | Pulse Repetition Frequency |
FUS-MB | Focused Ultrasound with Microbubbles Infusion |
References
- Si, Z.Z.; Zou, C.J.; Mei, X.; Li, X.F.; Luo, H.; Shen, Y.; Hu, J.; Li, X.X.; Wu, L.; Liu, Y. Targeting neuroinflammation in Alzheimer’s disease: From mechanisms to clinical applications. Neural Regen. Res. 2023, 18, 708–715. [Google Scholar] [PubMed]
- Sheng, J.; Zhang, S.; Wu, L.; Kumar, G.; Liao, Y.; Gk, P.; Fan, H. Inhibition of phosphodiesterase: A novel therapeutic target for the treatment of mild cognitive impairment and Alzheimer’s disease. Front. Aging Neurosci. 2022, 14, 1019187. [Google Scholar] [CrossRef] [PubMed]
- Moon, M.; Jung, E.S.; Jeon, S.G.; Cha, M.Y.; Jang, Y.; Kim, W.; Lopes, C.; Mook-Jung, I.; Kim, K.S. Nurr1 (NR4A2) regulates Alzheimer’s disease-related pathogenesis and cognitive function in the 5XFAD mouse model. Aging Cell 2019, 18, e12866. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cade, S.; Zhou, X.F.; Bobrovskaya, L. The role of brain-derived neurotrophic factor and the neurotrophin receptor p75NTR in age-related brain atrophy and the transition to Alzheimer’s disease. Rev. Neurosci. 2022, 33, 515–529. [Google Scholar] [CrossRef]
- Warren, S.L.; Moustafa, A.A. Functional magnetic resonance imaging, deep learning, and Alzheimer’s disease: A systematic review. J. Neuroimaging 2022. [Google Scholar] [CrossRef]
- Ayyubova, G. Dysfunctional microglia and tau pathology in Alzheimer’s disease. Rev. Neurosci. 2022. [Google Scholar] [CrossRef]
- Thal, D.R.; Tome, S.O. The central role of tau in Alzheimer’s disease: From neurofibrillary tangle maturation to the induction of cell death. Brain Res. Bull. 2022, 190, 204–217. [Google Scholar] [CrossRef]
- Xu, C.; Zhao, L.; Dong, C. A Review of Application of Abeta42/40 Ratio in Diagnosis and Prognosis of Alzheimer’s Disease. J. Alzheimers Dis. 2022, 90, 495–512. [Google Scholar] [CrossRef]
- Gong, B.; Ji, W.; Chen, X.; Li, P.; Cheng, W.; Zhao, Y.; He, B.; Zhuang, J.; Gao, J.; Yin, Y. Recent Advancements in Strategies for Abnormal Protein Clearance in Alzheimer’s Disease. Mini Rev. Med. Chem. 2022, 22, 2260–2270. [Google Scholar]
- Zuroff, L.; Daley, D.; Black, K.L.; Koronyo-Hamaoui, M. Clearance of cerebral Abeta in Alzheimer’s disease: Reassessing the role of microglia and monocytes. Cell. Mol. Life Sci. 2017, 74, 2167–2201. [Google Scholar] [CrossRef] [Green Version]
- Slater, C.; Wang, Q. Alzheimer’s disease: An evolving understanding of noradrenergic involvement and the promising future of electroceutical therapies. Clin. Transl. Med. 2021, 11, e397. [Google Scholar] [CrossRef] [PubMed]
- Magisetty, R.; Park, S.M. New Era of Electroceuticals: Clinically Driven Smart Implantable Electronic Devices Moving towards Precision Therapy. Micromachines 2022, 13, 161. [Google Scholar] [CrossRef] [PubMed]
- Long, Y.; Li, J.; Yang, F.; Wang, J.; Wang, X. Wearable and Implantable Electroceuticals for Therapeutic Electrostimulations. Adv. Sci. 2021, 8, 2004023. [Google Scholar] [CrossRef] [PubMed]
- Jang, Y.; Park, T.; Kim, E.; Park, J.W.; Lee, D.Y.; Kim, S.J. Implantable Biosupercapacitor Inspired by the Cellular Redox System. Angew. Chem. Int. Ed. Engl. 2021, 60, 10563–10567. [Google Scholar] [CrossRef]
- Luo, Y.; Yang, W.; Li, N.; Yang, X.; Zhu, B.; Wang, C.; Hou, W.; Wang, X.; Wen, H.; Tian, X. Anodal Transcranial Direct Current Stimulation Can Improve Spatial Learning and Memory and Attenuate Abeta42 Burden at the Early Stage of Alzheimer’s Disease in APP/PS1 Transgenic Mice. Front. Aging Neurosci. 2020, 12, 134. [Google Scholar] [CrossRef]
- Duan, M.; Meng, Z.; Yuan, D.; Zhang, Y.; Tang, T.; Chen, Z.; Fu, Y. Anodal and cathodal transcranial direct current stimulations of prefrontal cortex in a rodent model of Alzheimer’s disease. Front. Aging Neurosci. 2022, 14, 968451. [Google Scholar] [CrossRef]
- Yu, X.; Li, Y.; Wen, H.; Zhang, Y.; Tian, X. Intensity-dependent effects of repetitive anodal transcranial direct current stimulation on learning and memory in a rat model of Alzheimer’s disease. Neurobiol. Learn Mem. 2015, 123, 168–178. [Google Scholar] [CrossRef]
- Ruohonen, J.; Karhu, J. tDCS possibly stimulates glial cells. Clin. Neurophysiol. 2012, 123, 2006–2009. [Google Scholar] [CrossRef]
- Gondard, E.; Soto-Montenegro, M.L.; Cassol, A.; Lozano, A.M.; Hamani, C. Transcranial direct current stimulation does not improve memory deficits or alter pathological hallmarks in a rodent model of Alzheimer’s disease. J. Psychiatr. Res. 2019, 114, 93–98. [Google Scholar] [CrossRef]
- Luo, Y.P.; Liu, Z.; Wang, C.; Yang, X.F.; Wu, X.Y.; Tian, X.L.; Wen, H.Z. Anodal transcranial direct current stimulation alleviates cognitive impairment in an APP/PS1 model of Alzheimer’s disease in the preclinical stage. Neural Regen. Res. 2022, 17, 2278–2285. [Google Scholar]
- Luo, Y.; Yang, H.; Yan, X.; Wu, Y.; Wei, G.; Wu, X.; Tian, X.; Xiong, Y.; Wu, G.; Wen, H. Transcranial Direct Current Stimulation Alleviates Neurovascular Unit Dysfunction in Mice with Preclinical Alzheimer’s Disease. Front. Aging Neurosci. 2022, 14, 857415. [Google Scholar] [CrossRef] [PubMed]
- Marcello, E.; Borroni, B.; Pelucchi, S.; Gardoni, F.; Di Luca, M. ADAM10 as a therapeutic target for brain diseases: From developmental disorders to Alzheimer’s disease. Expert Opin. Ther. Targets 2017, 21, 1017–1026. [Google Scholar] [CrossRef] [PubMed]
- Pikhovych, A.; Stolberg, N.P.; Jessica Flitsch, L.; Walter, H.L.; Graf, R.; Fink, G.R.; Schroeter, M.; Rueger, M.A. Transcranial Direct Current Stimulation Modulates Neurogenesis and Microglia Activation in the Mouse Brain. Stem Cells Int. 2016, 2016, 2715196. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wachter, D.; Wrede, A.; Schulz-Schaeffer, W.; Taghizadeh-Waghefi, A.; Nitsche, M.A.; Kutschenko, A.; Rohde, V.; Liebetanz, D. Transcranial direct current stimulation induces polarity-specific changes of cortical blood perfusion in the rat. Exp. Neurol. 2011, 227, 322–327. [Google Scholar] [CrossRef] [PubMed]
- Lengu, K.; Ryan, S.; Peltier, S.J.; Tyszkowski, T.; Kairys, A.; Giordani, B.; Hampstead, B.M. Effects of High Definition-Transcranial Direct Current Stimulation on Local GABA and Glutamate Levels Among Older Adults with and without Mild Cognitive Impairment: An Exploratory Study. J. Alzheimers Dis. 2021, 84, 1091–1102. [Google Scholar] [CrossRef]
- Chen, J.; Wang, Z.; Chen, Q.; Fu, Y.; Zheng, K. Transcranial Direct Current Stimulation Enhances Cognitive Function in Patients with Mild Cognitive Impairment and Early/Mid Alzheimer’s Disease: A Systematic Review and Meta-Analysis. Brain Sci. 2022, 12, 562. [Google Scholar] [CrossRef]
- Simko, P.; Kent, J.A.; Rektorova, I. Is non-invasive brain stimulation effective for cognitive enhancement in Alzheimer’s disease? An updated meta-analysis. Clin. Neurophysiol. 2022, 144, 23–40. [Google Scholar] [CrossRef]
- Mondino, M.; Ghumman, S.; Gane, C.; Renauld, E.; Whittingstall, K.; Fecteau, S. Effects of Transcranial Stimulation with Direct and Alternating Current on Resting-State Functional Connectivity: An Exploratory Study Simultaneously Combining Stimulation and Multiband Functional Magnetic Resonance Imaging. Front. Hum. Neurosci. 2019, 13, 474. [Google Scholar] [CrossRef] [Green Version]
- Guidetti, M.; Bertini, A.; Pirone, F.; Sala, G.; Signorelli, P.; Ferrarese, C.; Priori, A.; Bocci, T. Neuroprotection and Non-Invasive Brain Stimulation: Facts or Fiction? Int. J. Mol. Sci. 2022, 23, 13775. [Google Scholar] [CrossRef]
- Bhattacharya, J.; Petsche, H. Phase synchrony analysis of EEG during music perception reveals changes in functional connectivity due to musical expertise. Signal Process. 2005, 85, 2161–2177. [Google Scholar] [CrossRef]
- Mably, A.J.; Colgin, L.L. Gamma oscillations in cognitive disorders. Curr. Opin. Neurobiol. 2018, 52, 182–187. [Google Scholar] [CrossRef] [PubMed]
- Wang, C.; Costanzo, M.E.; Rapp, P.E.; Darmon, D.; Nathan, D.E.; Bashirelahi, K.; Pham, D.L.; Roy, M.J.; Keyser, D.O. Disrupted Gamma Synchrony after Mild Traumatic Brain Injury and Its Correlation with White Matter Abnormality. Front. Neurol. 2017, 8, 571. [Google Scholar] [CrossRef]
- Iaccarino, H.F.; Singer, A.C.; Martorell, A.J.; Rudenko, A.; Gao, F.; Gillingham, T.Z.; Mathys, H.; Seo, J.; Kritskiy, O.; Abdurrob, F.; et al. Gamma frequency entrainment attenuates amyloid load and modifies microglia. Nature 2016, 540, 230–235. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Guan, A.; Wang, S.; Huang, A.; Qiu, C.; Li, Y.; Li, X.; Wang, J.; Wang, Q.; Deng, B. The role of gamma oscillations in central nervous system diseases: Mechanism and treatment. Front. Cell. Neurosci. 2022, 16, 962957. [Google Scholar] [CrossRef] [PubMed]
- Jafari, Z.; Kolb, B.E.; Mohajerani, M.H. Neural oscillations and brain stimulation in Alzheimer’s disease. Prog. Neurobiol. 2020, 194, 101878. [Google Scholar] [CrossRef]
- Chan, D.; Suk, H.J.; Jackson, B.; Milman, N.P.; Stark, D.; Beach, S.D.; Tsai, L.H. Induction of specific brain oscillations may restore neural circuits and be used for the treatment of Alzheimer’s disease. J. Intern. Med. 2021, 290, 993–1009. [Google Scholar] [CrossRef]
- He, Q.; Colon-Motas, K.M.; Pybus, A.F.; Piendel, L.; Seppa, J.K.; Walker, M.L.; Manzanares, C.M.; Qiu, D.; Miocinovic, S.; Wood, L.B.; et al. A feasibility trial of gamma sensory flicker for patients with prodromal Alzheimer’s disease. Alzheimers Dement. 2021, 7, e12178. [Google Scholar] [CrossRef]
- Lozano, A.M.; Hutchison, W.D.; Kalia, S.K. What Have We Learned about Movement Disorders from Functional Neurosurgery? Annu. Rev. Neurosci. 2017, 40, 453–477. [Google Scholar] [CrossRef] [PubMed]
- Herrington, T.M.; Cheng, J.J.; Eskandar, E.N. Mechanisms of deep brain stimulation. J. Neurophysiol. 2016, 115, 19–38. [Google Scholar] [CrossRef] [Green Version]
- Kanta, V.; Pare, D.; Headley, D.B. Closed-loop control of gamma oscillations in the amygdala demonstrates their role in spatial memory consolidation. Nat. Commun. 2019, 10, 3970. [Google Scholar] [CrossRef] [Green Version]
- Etter, G.; van der Veldt, S.; Manseau, F.; Zarrinkoub, I.; Trillaud-Doppia, E.; Williams, S. Optogenetic gamma stimulation rescues memory impairments in an Alzheimer’s disease mouse model. Nat. Commun. 2019, 10, 5322. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Dhaynaut, M.; Sprugnoli, G.; Cappon, D.; Macone, J.; Sanchez, J.S.; Normandin, M.D.; Guehl, N.J.; Koch, G.; Paciorek, R.; Connor, A.; et al. Impact of 40 Hz Transcranial Alternating Current Stimulation on Cerebral Tau Burden in Patients with Alzheimer’s Disease: A Case Series. J. Alzheimers Dis. 2022, 85, 1667–1676. [Google Scholar] [CrossRef] [PubMed]
- Broncel, A.; Bocian, R.; Klos-Wojtczak, P.; Kulbat-Warycha, K.; Konopacki, J. Vagal nerve stimulation as a promising tool in the improvement of cognitive disorders. Brain Res. Bull. 2020, 155, 37–47. [Google Scholar] [CrossRef] [PubMed]
- Vargas-Caballero, M.; Warming, H.; Walker, R.; Holmes, C.; Cruickshank, G.; Patel, B. Vagus Nerve Stimulation as a Potential Therapy in Early Alzheimer’s Disease: A Review. Front. Hum. Neurosci. 2022, 16, 866434. [Google Scholar] [CrossRef]
- Farmer, A.D.; Strzelczyk, A.; Finisguerra, A.; Gourine, A.V.; Gharabaghi, A.; Hasan, A.; Burger, A.M.; Jaramillo, A.M.; Mertens, A.; Majid, A.; et al. International Consensus Based Review and Recommendations for Minimum Reporting Standards in Research on Transcutaneous Vagus Nerve Stimulation (Version 2020). Front. Hum. Neurosci. 2020, 14, 568051. [Google Scholar] [CrossRef]
- Giordano, F.; Zicca, A.; Barba, C.; Guerrini, R.; Genitori, L. Vagus nerve stimulation: Surgical technique of implantation and revision and related morbidity. Epilepsia 2017, 58 (Suppl. 1), 85–90. [Google Scholar] [CrossRef]
- Yu, Y.; Jiang, X.; Fang, X.; Wang, Y.; Liu, P.; Ling, J.; Yu, L.; Jiang, M.; Tang, C. Transauricular Vagal Nerve Stimulation at 40 Hz Inhibits Hippocampal P2X7R/NLRP3/Caspase-1 Signaling and Improves Spatial Learning and Memory in 6-Month-Old APP/PS1 Mice. Neuromodulation 2022. [Google Scholar] [CrossRef]
- Sun, K.; Zhang, J.; Yang, Q.; Zhu, J.; Zhang, X.; Wu, K.; Li, Z.; Xie, W.; Luo, X. Dexmedetomidine exerts a protective effect on ischemic brain injury by inhibiting the P2X7R/NLRP3/Caspase-1 signaling pathway. Brain Res. Bull. 2021, 174, 11–21. [Google Scholar] [CrossRef]
- Uzair, M.; Abualait, T.; Arshad, M.; Yoo, W.K.; Mir, A.; Bunyan, R.F.; Bashir, S. Transcranial magnetic stimulation in animal models of neurodegeneration. Neural Regen. Res. 2022, 17, 251–265. [Google Scholar]
- Cuypers, K.; Marsman, A. Transcranial magnetic stimulation and magnetic resonance spectroscopy: Opportunities for a bimodal approach in human neuroscience. Neuroimage 2021, 224, 117394. [Google Scholar] [CrossRef]
- Chervyakov, A.V.; Chernyavsky, A.Y.; Sinitsyn, D.O.; Piradov, M.A. Possible Mechanisms Underlying the Therapeutic Effects of Transcranial Magnetic Stimulation. Front. Hum. Neurosci. 2015, 9, 303. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Eldaief, M.C.; Press, D.Z.; Pascual-Leone, A. Transcranial magnetic stimulation in neurology: A review of established and prospective applications. Neurol Clin. Pract. 2013, 3, 519–526. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Moussavi, Z.; Rutherford, G.; Lithgow, B.; Millikin, C.; Modirrousta, M.; Mansouri, B.; Wang, X.; Omelan, C.; Fellows, L.; Fitzgerald, P.; et al. Repeated Transcranial Magnetic Stimulation for Improving Cognition in Patients With Alzheimer Disease: Protocol for a Randomized, Double-Blind, Placebo-Controlled Trial. JMIR Res. Protoc. 2021, 10, e25144. [Google Scholar] [CrossRef] [PubMed]
- Li, X.; Qi, G.; Yu, C.; Lian, G.; Zheng, H.; Wu, S.; Yuan, T.F.; Zhou, D. Cortical plasticity is correlated with cognitive improvement in Alzheimer’s disease patients after rTMS treatment. Brain Stimul. 2021, 14, 503–510. [Google Scholar] [CrossRef] [PubMed]
- Wang, F.; Zhang, Y.; Wang, L.; Sun, P.; Luo, X.; Ishigaki, Y.; Sugai, T.; Yamamoto, R.; Kato, N. Improvement of spatial learning by facilitating large-conductance calcium-activated potassium channel with transcranial magnetic stimulation in Alzheimer’s disease model mice. Neuropharmacology 2015, 97, 210–219. [Google Scholar] [CrossRef]
- Stock, M.; Kirchner, B.; Waibler, D.; Cowley, D.E.; Pfaffl, M.W.; Kuehn, R. Effect of magnetic stimulation on the gene expression profile of in vitro cultured neural cells. Neurosci. Lett. 2012, 526, 122–127. [Google Scholar] [CrossRef]
- Chen, X.; Chen, S.; Liang, W.; Ba, F. Administration of Repetitive Transcranial Magnetic Stimulation Attenuates Abeta 1-42-Induced Alzheimer’s Disease in Mice by Activating beta-Catenin Signaling. BioMed Res. Int. 2019, 2019, 1431760. [Google Scholar]
- Jang, Y.; Lee, S.H.; Lee, B.; Jung, S.; Khalid, A.; Uchida, K.; Tominaga, M.; Jeon, D.; Oh, U. TRPM2, a Susceptibility Gene for Bipolar Disorder, Regulates Glycogen Synthase Kinase-3 Activity in the Brain. J. Neurosci. 2015, 35, 11811–11823. [Google Scholar] [CrossRef]
- Ba, F.; Zhou, Y.; Zhou, J.; Chen, X. Repetitive transcranial magnetic stimulation protects mice against 6-OHDA-induced Parkinson’s disease symptoms by regulating brain amyloid beta1-42 level. Mol. Cell. Biochem. 2019, 458, 71–78. [Google Scholar] [CrossRef]
- Jang, Y.; Kim, W.; Leblanc, P.; Kim, C.H.; Kim, K.S. Potent synthetic and endogenous ligands for the adopted orphan nuclear receptor Nurr1. Exp. Mol. Med. 2021, 53, 19–29. [Google Scholar] [CrossRef]
- Rajan, S.; Jang, Y.; Kim, C.H.; Kim, W.; Toh, H.T.; Jeon, J.; Song, B.; Serra, A.; Lescar, J.; Yoo, J.Y.; et al. PGE1 and PGA1 bind to Nurr1 and activate its transcriptional function. Nat. Chem. Biol. 2020, 16, 876–886. [Google Scholar] [CrossRef] [PubMed]
- Chen, X.; Dong, G.Y.; Wang, L.X. High-frequency transcranial magnetic stimulation protects APP/PS1 mice against Alzheimer’s disease progress by reducing APOE and enhancing autophagy. Brain Behav. 2020, 10, e01740. [Google Scholar] [CrossRef] [PubMed]
- Lin, Y.; Jin, J.; Lv, R.; Luo, Y.; Dai, W.; Li, W.; Tang, Y.; Wang, Y.; Ye, X.; Lin, W.J. Repetitive transcranial magnetic stimulation increases the brain’s drainage efficiency in a mouse model of Alzheimer’s disease. Acta Neuropathol. Commun. 2021, 9, 102. [Google Scholar] [CrossRef] [PubMed]
- Cao, H.; Zuo, C.; Gu, Z.; Huang, Y.; Yang, Y.; Zhu, L.; Jiang, Y.; Wang, F. High frequency repetitive transcranial magnetic stimulation alleviates cognitive deficits in 3xTg-AD mice by modulating the PI3K/Akt/GLT-1 axis. Redox Biol. 2022, 54, 102354. [Google Scholar] [CrossRef] [PubMed]
- Buch, B.; Touyz, L.Z. The electromagnetic spectrum and the dentist. A biophysical review. Aust. Dent. J. 1987, 32, 159–165. [Google Scholar] [CrossRef]
- Ahmad, R.; Fakhoury, M.; Lawand, N. Electromagnetic Field in Alzheimer’s Disease: A Literature Review of Recent Preclinical and Clinical Studies. Curr. Alzheimer Res. 2020, 17, 1001–1012. [Google Scholar] [CrossRef]
- Perez, F.P.; Bandeira, J.P.; Perez Chumbiauca, C.N.; Lahiri, D.K.; Morisaki, J.; Rizkalla, M. Multidimensional insights into the repeated electromagnetic field stimulation and biosystems interaction in aging and age-related diseases. J. Biomed. Sci. 2022, 29, 39. [Google Scholar] [CrossRef]
- Jiang, D.P.; Li, J.H.; Zhang, J.; Xu, S.L.; Kuang, F.; Lang, H.Y.; Wang, Y.F.; An, G.Z.; Li, J.; Guo, G.Z. Long-term electromagnetic pulse exposure induces Abeta deposition and cognitive dysfunction through oxidative stress and overexpression of APP and BACE1. Brain Res. 2016, 1642, 10–19. [Google Scholar] [CrossRef]
- Jiang, D.P.; Li, J.; Zhang, J.; Xu, S.L.; Kuang, F.; Lang, H.Y.; Wang, Y.F.; An, G.Z.; Li, J.H.; Guo, G.Z. Electromagnetic pulse exposure induces overexpression of beta amyloid protein in rats. Arch Med. Res. 2013, 44, 178–184. [Google Scholar] [CrossRef]
- Arendash, G.W. Review of the Evidence that Transcranial Electromagnetic Treatment will be a Safe and Effective Therapeutic Against Alzheimer’s Disease. J. Alzheimers Dis. 2016, 53, 753–771. [Google Scholar] [CrossRef] [Green Version]
- Del Giudice, E.; Facchinetti, F.; Nofrate, V.; Boccaccio, P.; Minelli, T.; Dam, M.; Leon, A.; Moschini, G. Fifty Hertz electromagnetic field exposure stimulates secretion of beta-amyloid peptide in cultured human neuroglioma. Neurosci. Lett. 2007, 418, 9–12. [Google Scholar] [CrossRef] [PubMed]
- Zhang, Y.; Liu, X.; Zhang, J.; Li, N. Short-term effects of extremely low frequency electromagnetic fields exposure on Alzheimer’s disease in rats. Int. J. Radiat. Biol. 2015, 91, 28–34. [Google Scholar] [CrossRef] [PubMed]
- Perez, F.P.; Maloney, B.; Chopra, N.; Morisaki, J.J.; Lahiri, D.K. Repeated electromagnetic field stimulation lowers amyloid-beta peptide levels in primary human mixed brain tissue cultures. Sci. Rep. 2021, 11, 621. [Google Scholar] [CrossRef] [PubMed]
- Tsoy, A.; Saliev, T.; Abzhanova, E.; Turgambayeva, A.; Kaiyrlykyzy, A.; Akishev, M.; Saparbayev, S.; Umbayev, B.; Askarova, S. The Effects of Mobile Phone Radiofrequency Electromagnetic Fields on beta-Amyloid-Induced Oxidative Stress in Human and Rat Primary Astrocytes. Neuroscience 2019, 408, 46–57. [Google Scholar] [CrossRef]
- Arendash, G.W.; Mori, T.; Dorsey, M.; Gonzalez, R.; Tajiri, N.; Borlongan, C. Electromagnetic treatment to old Alzheimer’s mice reverses beta-amyloid deposition, modifies cerebral blood flow, and provides selected cognitive benefit. PLoS ONE 2012, 7, e35751. [Google Scholar] [CrossRef] [Green Version]
- Jeong, Y.J.; Kang, G.Y.; Kwon, J.H.; Choi, H.D.; Pack, J.K.; Kim, N.; Lee, Y.S.; Lee, H.J. 1950 MHz Electromagnetic Fields Ameliorate Abeta Pathology in Alzheimer’s Disease Mice. Curr. Alzheimer Res. 2015, 12, 481–492. [Google Scholar] [CrossRef]
- Son, Y.; Jeong, Y.J.; Kwon, J.H.; Choi, H.D.; Pack, J.K.; Kim, N.; Lee, Y.S.; Lee, H.J. 1950 MHz radiofrequency electromagnetic fields do not aggravate memory deficits in 5xFAD mice. Bioelectromagnetics 2016, 37, 391–399. [Google Scholar] [CrossRef]
- Arendash, G.; Abulaban, H.; Steen, S.; Andel, R.; Wang, Y.; Bai, Y.; Baranowski, R.; McGarity, J.; Scritsmier, L.; Lin, X.; et al. Transcranial Electromagnetic Treatment Stops Alzheimer’s Disease Cognitive Decline over a 2(1/2)-Year Period: A Pilot Study. Medicines 2022, 9, 42. [Google Scholar] [CrossRef]
- Iqbal, K.; Gong, C.X.; Liu, F. Hyperphosphorylation-induced tau oligomers. Front. Neurol. 2013, 4, 112. [Google Scholar] [CrossRef] [Green Version]
- Passarella, S.; Karu, T. Absorption of monochromatic and narrow band radiation in the visible and near IR by both mitochondrial and non-mitochondrial photoacceptors results in photobiomodulation. J. Photochem. Photobiol. B 2014, 140, 344–358. [Google Scholar] [CrossRef]
- Bashkatov, A.N.; Genina, E.; Kochubey, V.; Tuchin, V. Optical properties of human skin, subcutaneous and mucous tissues in the wavelength range from 400 to 2000 nm. J. Phys. D Appl. Phys. 2005, 38, 2543. [Google Scholar] [CrossRef]
- Grillo, S.L.; Duggett, N.A.; Ennaceur, A.; Chazot, P.L. Non-invasive infra-red therapy (1072 nm) reduces beta-amyloid protein levels in the brain of an Alzheimer’s disease mouse model, TASTPM. J. Photochem. Photobiol. B 2013, 123, 13–22. [Google Scholar] [CrossRef] [PubMed]
- Narayanan, S.; Kamps, B.; Boelens, W.C.; Reif, B. alphaB-crystallin competes with Alzheimer’s disease beta-amyloid peptide for peptide-peptide interactions and induces oxidation of Abeta-Met35. FEBS Lett. 2006, 580, 5941–5946. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Purushothuman, S.; Johnstone, D.M.; Nandasena, C.; van Eersel, J.; Ittner, L.M.; Mitrofanis, J.; Stone, J. Near infrared light mitigates cerebellar pathology in transgenic mouse models of dementia. Neurosci. Lett. 2015, 591, 155–159. [Google Scholar] [CrossRef]
- Stepanov, Y.V.; Golovynska, I.; Zhang, R.; Golovynskyi, S.; Stepanova, L.I.; Gorbach, O.; Dovbynchuk, T.; Garmanchuk, L.V.; Ohulchanskyy, T.Y.; Qu, J. Near-infrared light reduces beta-amyloid-stimulated microglial toxicity and enhances survival of neurons: Mechanisms of light therapy for Alzheimer’s disease. Alzheimers Res. Ther. 2022, 14, 84. [Google Scholar] [CrossRef]
- Vatansever, F.; Hamblin, M.R. Far infrared radiation (FIR): Its biological effects and medical applications. Photonics Lasers Med. 2012, 4, 255–266. [Google Scholar] [CrossRef] [Green Version]
- Li, Q.; Peng, J.; Luo, Y.; Zhou, J.; Li, T.; Cao, L.; Peng, S.; Zuo, Z.; Wang, Z. Far infrared light irradiation enhances Abeta clearance via increased exocytotic microglial ATP and ameliorates cognitive deficit in Alzheimer’s disease-like mice. J. Neuroinflamm. 2022, 19, 145. [Google Scholar] [CrossRef]
- Siegel, J.A.; Greenspan, B.S.; Maurer, A.H.; Taylor, A.T.; Phillips, W.T.; Van Nostrand, D.; Sacks, B.; Silberstein, E.B. The BEIR VII Estimates of Low-Dose Radiation Health Risks Are Based on Faulty Assumptions and Data Analyses: A Call for Reassessment. J. Nucl. Med. 2018, 59, 1017–1019. [Google Scholar] [CrossRef] [Green Version]
- Sharma, N.K.; Sharma, R.; Mathur, D.; Sharad, S.; Minhas, G.; Bhatia, K.; Anand, A.; Ghosh, S.P. Role of Ionizing Radiation in Neurodegenerative Diseases. Front. Aging Neurosci. 2018, 10, 134. [Google Scholar] [CrossRef] [Green Version]
- Khandelwal, M.; Manglani, K.; Gupta, S.; Tiku, A.B. Gamma radiation improves AD pathogenesis in APP/PS1 mouse model by potentiating insulin sensitivity. Heliyon 2020, 6, e04499. [Google Scholar] [CrossRef]
- Hwang, S.; Jeong, H.; Hong, E.H.; Joo, H.M.; Cho, K.S.; Nam, S.Y. Low-dose ionizing radiation alleviates Abeta42-induced cell death via regulating AKT and p38 pathways in Drosophila Alzheimer’s disease models. Biol. Open 2019, 8, bio036657. [Google Scholar] [CrossRef] [Green Version]
- McRobb, L.S.; McKay, M.J.; Gamble, J.R.; Grace, M.; Moutrie, V.; Santos, E.D.; Lee, V.S.; Zhao, Z.; Molloy, M.P.; Stoodley, M.A. Ionizing radiation reduces ADAM10 expression in brain microvascular endothelial cells undergoing stress-induced senescence. Aging 2017, 9, 1248–1268. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rudobeck, E.; Bellone, J.A.; Szucs, A.; Bonnick, K.; Mehrotra-Carter, S.; Badaut, J.; Nelson, G.A.; Hartman, R.E.; Vlkolinsky, R. Low-dose proton radiation effects in a transgenic mouse model of Alzheimer’s disease—Implications for space travel. PLoS ONE 2017, 12, e0186168. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Li, L.; Wang, W.; Welford, S.; Zhang, T.; Wang, X.; Zhu, X. Ionizing radiation causes increased tau phosphorylation in primary neurons. J. Neurochem. 2014, 131, 86–93. [Google Scholar] [CrossRef]
- Cherry, J.D.; Liu, B.; Frost, J.L.; Lemere, C.A.; Williams, J.P.; Olschowka, J.A.; O’Banion, M.K. Galactic cosmic radiation leads to cognitive impairment and increased abeta plaque accumulation in a mouse model of Alzheimer’s disease. PLoS ONE 2012, 7, e53275. [Google Scholar] [CrossRef] [Green Version]
- Vlkolinsky, R.; Titova, E.; Krucker, T.; Chi, B.B.; Staufenbiel, M.; Nelson, G.A.; Obenaus, A. Exposure to 56Fe-particle radiation accelerates electrophysiological alterations in the hippocampus of APP23 transgenic mice. Radiat. Res. 2010, 173, 342–352. [Google Scholar] [CrossRef] [PubMed]
- Azizova, T.V.; Muirhead, C.R.; Druzhinina, M.B.; Grigoryeva, E.S.; Vlasenko, E.V.; Sumina, M.V.; O’Hagan, J.A.; Zhang, W.; Haylock, R.G.; Hunter, N. Cerebrovascular diseases in the cohort of workers first employed at Mayak PA in 1948–1958. Radiat. Res. 2010, 174, 851–864. [Google Scholar] [CrossRef]
- Fike, J.R.; Rola, R.; Limoli, C.L. Radiation response of neural precursor cells. Neurosurg. Clin. N. Am. 2007, 18, 115–127. [Google Scholar] [CrossRef]
- Lowe, X.R.; Bhattacharya, S.; Marchetti, F.; Wyrobek, A.J. Early brain response to low-dose radiation exposure involves molecular networks and pathways associated with cognitive functions, advanced aging and Alzheimer’s disease. Radiat. Res. 2009, 171, 53–65. [Google Scholar] [CrossRef] [Green Version]
- Ceyzeriat, K.; Tournier, B.B.; Millet, P.; Dipasquale, G.; Koutsouvelis, N.; Frisoni, G.B.; Garibotto, V.; Zilli, T. Low-Dose Radiation Therapy Reduces Amyloid Load in Young 3xTg-AD Mice. J. Alzheimers Dis. 2022, 86, 641–653. [Google Scholar] [CrossRef]
- Kim, S.; Chung, H.; Ngoc Mai, H.; Nam, Y.; Shin, S.J.; Park, Y.H.; Chung, M.J.; Lee, J.K.; Rhee, H.Y.; Jahng, G.H.; et al. Low-Dose Ionizing Radiation Modulates Microglia Phenotypes in the Models of Alzheimer’s Disease. Int. J. Mol. Sci. 2020, 21, 4532. [Google Scholar] [CrossRef] [PubMed]
- Marples, B.; McGee, M.; Callan, S.; Bowen, S.E.; Thibodeau, B.J.; Michael, D.B.; Wilson, G.D.; Maddens, M.E.; Fontanesi, J.; Martinez, A.A. Cranial irradiation significantly reduces beta amyloid plaques in the brain and improves cognition in a murine model of Alzheimer’s Disease (AD). Radiother. Oncol. 2016, 118, 579–580. [Google Scholar] [CrossRef] [PubMed]
- Yang, E.J.; Kim, H.; Choi, Y.; Kim, H.J.; Kim, J.H.; Yoon, J.; Seo, Y.S.; Kim, H.S. Modulation of Neuroinflammation by Low-Dose Radiation Therapy in an Animal Model of Alzheimer’s Disease. Int. J. Radiat. Oncol. Biol. Phys. 2021, 111, 658–670. [Google Scholar] [CrossRef]
- Wilson, G.D.; Wilson, T.G.; Hanna, A.; Fontanesi, G.; Kulchycki, J.; Buelow, K.; Pruetz, B.L.; Michael, D.B.; Chinnaiyan, P.; Maddens, M.E.; et al. Low Dose Brain Irradiation Reduces Amyloid-beta and Tau in 3xTg-AD Mice. J. Alzheimers Dis. 2020, 75, 15–21. [Google Scholar] [CrossRef] [PubMed]
- Owlett, L.; Belcher, E.K.; Dionisio-Santos, D.A.; Williams, J.P.; Olschowka, J.A.; O’Banion, M.K. Space radiation does not alter amyloid or tau pathology in the 3xTg mouse model of Alzheimer’s disease. Life Sci. Space Res. 2020, 27, 89–98. [Google Scholar] [CrossRef]
- Ceyzeriat, K.; Zilli, T.; Fall, A.B.; Millet, P.; Koutsouvelis, N.; Dipasquale, G.; Frisoni, G.B.; Tournier, B.B.; Garibotto, V. Treatment by low-dose brain radiation therapy improves memory performances without changes of the amyloid load in the TgF344-AD rat model. Neurobiol. Aging 2021, 103, 117–127. [Google Scholar] [CrossRef]
- Kim, S.; Nam, Y.; Kim, C.; Lee, H.; Hong, S.; Kim, H.S.; Shin, S.J.; Park, Y.H.; Mai, H.N.; Oh, S.M.; et al. Neuroprotective and Anti-Inflammatory Effects of Low-Moderate Dose Ionizing Radiation in Models of Alzheimer’s Disease. Int. J. Mol. Sci. 2020, 21, 3678. [Google Scholar] [CrossRef]
- Lin, W.T.; Chen, R.C.; Lu, W.W.; Liu, S.H.; Yang, F.Y. Protective effects of low-intensity pulsed ultrasound on aluminum-induced cerebral damage in Alzheimer’s disease rat model. Sci. Rep. 2015, 5, 9671. [Google Scholar] [CrossRef] [Green Version]
- Eguchi, K.; Shindo, T.; Ito, K.; Ogata, T.; Kurosawa, R.; Kagaya, Y.; Monma, Y.; Ichijo, S.; Kasukabe, S.; Miyata, S.; et al. Whole-brain low-intensity pulsed ultrasound therapy markedly improves cognitive dysfunctions in mouse models of dementia—Crucial roles of endothelial nitric oxide synthase. Brain Stimul. 2018, 11, 959–973. [Google Scholar] [CrossRef] [Green Version]
- Bobola, M.S.; Chen, L.; Ezeokeke, C.K.; Olmstead, T.A.; Nguyen, C.; Sahota, A.; Williams, R.G.; Mourad, P.D. Transcranial focused ultrasound, pulsed at 40 Hz, activates microglia acutely and reduces Abeta load chronically, as demonstrated in vivo. Brain Stimul. 2020, 13, 1014–1023. [Google Scholar] [CrossRef]
- Leinenga, G.; Koh, W.K.; Gotz, J. Scanning ultrasound in the absence of blood-brain barrier opening is not sufficient to clear beta-amyloid plaques in the APP23 mouse model of Alzheimer’s disease. Brain Res. Bull. 2019, 153, 8–14. [Google Scholar] [CrossRef] [PubMed]
- Gotz, J.; Richter-Stretton, G.; Cruz, E. Therapeutic Ultrasound as a Treatment Modality for Physiological and Pathological Ageing Including Alzheimer’s Disease. Pharmaceutics 2021, 13, 1002. [Google Scholar] [CrossRef] [PubMed]
- Lee, Y.; Choi, Y.; Park, E.J.; Kwon, S.; Kim, H.; Lee, J.Y.; Lee, D.S. Improvement of glymphatic-lymphatic drainage of beta-amyloid by focused ultrasound in Alzheimer’s disease model. Sci. Rep. 2020, 10, 16144. [Google Scholar] [CrossRef]
- Pandit, R.; Leinenga, G.; Gotz, J. Repeated ultrasound treatment of tau transgenic mice clears neuronal tau by autophagy and improves behavioral functions. Theranostics 2019, 9, 3754–3767. [Google Scholar] [CrossRef] [PubMed]
- Karakatsani, M.E.; Kugelman, T.; Ji, R.; Murillo, M.; Wang, S.; Niimi, Y.; Small, S.A.; Duff, K.E.; Konofagou, E.E. Unilateral Focused Ultrasound-Induced Blood-Brain Barrier Opening Reduces Phosphorylated Tau from The rTg4510 Mouse Model. Theranostics 2019, 9, 5396–5411. [Google Scholar] [CrossRef]
- Poon, C.T.; Shah, K.; Lin, C.; Tse, R.; Kim, K.K.; Mooney, S.; Aubert, I.; Stefanovic, B.; Hynynen, K. Time course of focused ultrasound effects on beta-amyloid plaque pathology in the TgCRND8 mouse model of Alzheimer’s disease. Sci. Rep. 2018, 8, 14061. [Google Scholar] [CrossRef] [Green Version]
- Leinenga, G.; Gotz, J. Safety and Efficacy of Scanning Ultrasound Treatment of Aged APP23 Mice. Front. Neurosci. 2018, 12, 55. [Google Scholar] [CrossRef] [Green Version]
- Burgess, A.; Dubey, S.; Yeung, S.; Hough, O.; Eterman, N.; Aubert, I.; Hynynen, K. Alzheimer disease in a mouse model: MR imaging-guided focused ultrasound targeted to the hippocampus opens the blood-brain barrier and improves pathologic abnormalities and behavior. Radiology 2014, 273, 736–745. [Google Scholar] [CrossRef] [Green Version]
- Jordao, J.F.; Thevenot, E.; Markham-Coultes, K.; Scarcelli, T.; Weng, Y.Q.; Xhima, K.; O’Reilly, M.; Huang, Y.; McLaurin, J.; Hynynen, K.; et al. Amyloid-beta plaque reduction, endogenous antibody delivery and glial activation by brain-targeted, transcranial focused ultrasound. Exp. Neurol. 2013, 248, 16–29. [Google Scholar] [CrossRef] [Green Version]
- Leinenga, G.; Gotz, J. Scanning ultrasound removes amyloid-beta and restores memory in an Alzheimer’s disease mouse model. Sci. Transl. Med. 2015, 7, 278ra33. [Google Scholar] [CrossRef] [Green Version]
- Shen, Y.; Hua, L.; Yeh, C.K.; Shen, L.; Ying, M.; Zhang, Z.; Liu, G.; Li, S.; Chen, S.; Chen, X.; et al. Ultrasound with microbubbles improves memory, ameliorates pathology and modulates hippocampal proteomic changes in a triple transgenic mouse model of Alzheimer’s disease. Theranostics 2020, 10, 11794–11819. [Google Scholar] [CrossRef]
- Jang, Y.; Lee, B.; Kim, H.; Jung, S.; Lee, S.H.; Lee, S.Y.; Jeon, J.H.; Kim, I.B.; Lee, S.H.; Kim, B.J.; et al. Trpm2 Ablation Accelerates Protein Aggregation by Impaired ADPR and Autophagic Clearance in the Brain. Mol. Neurobiol. 2019, 56, 3819–3832. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lipsman, N.; Meng, Y.; Bethune, A.J.; Huang, Y.; Lam, B.; Masellis, M.; Herrmann, N.; Heyn, C.; Aubert, I.; Boutet, A.; et al. Blood-brain barrier opening in Alzheimer’s disease using MR-guided focused ultrasound. Nat. Commun. 2018, 9, 2336. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rezai, A.R.; Ranjan, M.; D’Haese, P.F.; Haut, M.W.; Carpenter, J.; Najib, U.; Mehta, R.I.; Chazen, J.L.; Zibly, Z.; Yates, J.R.; et al. Noninvasive hippocampal blood-brain barrier opening in Alzheimer’s disease with focused ultrasound. Proc. Natl. Acad. Sci. USA 2020, 117, 9180–9182. [Google Scholar] [CrossRef] [PubMed]
- D’Haese, P.F.; Ranjan, M.; Song, A.; Haut, M.W.; Carpenter, J.; Dieb, G.; Najib, U.; Wang, P.; Mehta, R.I.; Chazen, J.L.; et al. beta-Amyloid Plaque Reduction in the Hippocampus after Focused Ultrasound-Induced Blood-Brain Barrier Opening in Alzheimer’s Disease. Front. Hum. Neurosci. 2020, 14, 593672. [Google Scholar] [CrossRef] [PubMed]
- Epelbaum, S.; Burgos, N.; Canney, M.; Matthews, D.; Houot, M.; Santin, M.D.; Desseaux, C.; Bouchoux, G.; Stroer, S.; Martin, C.; et al. Pilot study of repeated blood-brain barrier disruption in patients with mild Alzheimer’s disease with an implantable ultrasound device. Alzheimers Res. Ther. 2022, 14, 40. [Google Scholar] [CrossRef] [PubMed]
- Raymond, S.B.; Treat, L.H.; Dewey, J.D.; McDannold, N.J.; Hynynen, K.; Bacskai, B.J. Ultrasound enhanced delivery of molecular imaging and therapeutic agents in Alzheimer’s disease mouse models. PLoS ONE 2008, 3, e2175. [Google Scholar] [CrossRef] [Green Version]
- Dubey, S.; Heinen, S.; Krantic, S.; McLaurin, J.; Branch, D.R.; Hynynen, K.; Aubert, I. Clinically approved IVIg delivered to the hippocampus with focused ultrasound promotes neurogenesis in a model of Alzheimer’s disease. Proc. Natl. Acad. Sci. USA 2020, 117, 32691–32700. [Google Scholar] [CrossRef]
- Jordao, J.F.; Ayala-Grosso, C.A.; Markham, K.; Huang, Y.; Chopra, R.; McLaurin, J.; Hynynen, K.; Aubert, I. Antibodies targeted to the brain with image-guided focused ultrasound reduces amyloid-beta plaque load in the TgCRND8 mouse model of Alzheimer’s disease. PLoS ONE 2010, 5, e10549. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Liu, M.; Jevtic, S.; Markham-Coultes, K.; Ellens, N.P.K.; O’Reilly, M.A.; Hynynen, K.; Aubert, I.; McLaurin, J. Investigating the efficacy of a combination Abeta-targeted treatment in a mouse model of Alzheimer’s disease. Brain Res. 2018, 1678, 138–145. [Google Scholar] [CrossRef]
- Alecou, T.; Giannakou, M.; Damianou, C. Amyloid beta Plaque Reduction with Antibodies Crossing the Blood-Brain Barrier, Which Was Opened in 3 Sessions of Focused Ultrasound in a Rabbit Model. J. Ultrasound Med. 2017, 36, 2257–2270. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sun, T.; Shi, Q.; Zhang, Y.; Power, C.; Hoesch, C.; Antonelli, S.; Schroeder, M.K.; Caldarone, B.J.; Taudte, N.; Schenk, M.; et al. Focused ultrasound with anti-pGlu3 Abeta enhances efficacy in Alzheimer’s disease-like mice via recruitment of peripheral immune cells. J. Control. Release 2021, 336, 443–456. [Google Scholar] [CrossRef] [PubMed]
- Nisbet, R.M.; Van der Jeugd, A.; Leinenga, G.; Evans, H.T.; Janowicz, P.W.; Gotz, J. Combined effects of scanning ultrasound and a tau-specific single chain antibody in a tau transgenic mouse model. Brain 2017, 140, 1220–1230. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hsu, P.H.; Lin, Y.T.; Chung, Y.H.; Lin, K.J.; Yang, L.Y.; Yen, T.C.; Liu, H.L. Focused Ultrasound-Induced Blood-Brain Barrier Opening Enhances GSK-3 Inhibitor Delivery for Amyloid-Beta Plaque Reduction. Sci. Rep. 2018, 8, 12882. [Google Scholar] [CrossRef]
- Liu, Y.; Gong, Y.; Xie, W.; Huang, A.; Yuan, X.; Zhou, H.; Zhu, X.; Chen, X.; Liu, J.; Liu, J.; et al. Microbubbles in combination with focused ultrasound for the delivery of quercetin-modified sulfur nanoparticles through the blood brain barrier into the brain parenchyma and relief of endoplasmic reticulum stress to treat Alzheimer’s disease. Nanoscale 2020, 12, 6498–6511. [Google Scholar] [CrossRef]
- Janowicz, P.W.; Leinenga, G.; Gotz, J.; Nisbet, R.M. Ultrasound-mediated blood-brain barrier opening enhances delivery of therapeutically relevant formats of a tau-specific antibody. Sci. Rep. 2019, 9, 9255. [Google Scholar] [CrossRef] [Green Version]
- Xu, M.; Zhou, H.; Liu, Y.; Sun, J.; Xie, W.; Zhao, P.; Liu, J. Ultrasound-Excited Protoporphyrin IX-Modified Multifunctional Nanoparticles as a Strong Inhibitor of Tau Phosphorylation and beta-Amyloid Aggregation. ACS Appl. Mater. Interfaces 2018, 10, 32965–32980. [Google Scholar] [CrossRef]
- Luo, K.; Wang, Y.; Chen, W.S.; Feng, X.; Liao, Y.; Chen, S.; Liu, Y.; Liao, C.; Chen, M.; Ao, L. Treatment Combining Focused Ultrasound with Gastrodin Alleviates Memory Deficit and Neuropathology in an Alzheimer’s Disease-like Experimental Mouse Model. Neural Plast. 2022, 2022, 5241449. [Google Scholar] [CrossRef]
- Weber-Adrian, D.; Kofoed, R.H.; Chan, J.W.Y.; Silburt, J.; Noroozian, Z.; Kugler, S.; Hynynen, K.; Aubert, I. Strategy to enhance transgene expression in proximity of amyloid plaques in a mouse model of Alzheimer’s disease. Theranostics 2019, 9, 8127–8137. [Google Scholar] [CrossRef]
Type of rTMS | Stimulation Intensity and Frequency | Duration | Subject | Main Finding | Reference |
---|---|---|---|---|---|
Chronic TMS | 80% of the maximum output of machine (MRS1000/50) 1, 10, 15 Hz | Pulse uprise time: 60 μs Pulse duration: 250 μs 5 s once a day for 4 weeks | 3xTg mice | - ↑ Homer1a expression - ↑ BK channel activity - ↓ Aβ42 level - ↑ hippocampal LTP | [52] |
1.26 T, 2 s inter-train interval, 1 and 10 Hz | 14 consecutive days | Aβ1-42 injected mice | - ↓ GSK-3β and phosphorylation of tau - ↑ β-catenin signaling - ↑ survival of neurons | [56] | |
1.26 T, 2 s inter-train interval, 1 and 10 Hz | 14 consecutive days | 6-OHDA-induced mice | - ↓ MKK7-ERK1/2-c-FOS-APP axis - ↓ Amyloid precursor protein level - ↓ Aβ42 level in brain tissues - ↑ cognitive behaviors | [59] | |
120% of the average resting motor threshold (CCY-3) Total 600 pulses (20 bursts, 30 pulses each train) 2 s inter-train interval, 5 Hz | 14 consecutive days | APP/PS1 mice | - ↓ ApoE, p62 and PP2A expressions - ↑ Aβ, APP and pTau levels - ↑ hippocampal autophagy - ↑ spatial, cognitive learning and memory | [62] | |
1.38 T, 100 sessions (40 bursts trains), 5 s inter-session interval 20 Hz | 14 consecutive days | 5xFAD mice | - ↓ active glial cells (microglia and astrocytes) - ↑ neuronal activity | [63] | |
60% of the maximum output of machine (MRS1000/50) Total 1000 pulses (10 trains of 100 pulses) 25 s inter-train interval, 25 Hz | 28 consecutive days | 3xTg mice | - ↓ hippocampal Aβ42 levels - ↑ PI3K and Akt signals - ↑ alleviation of cognitive deficits | [64] |
Type of EMF | Stimulation Intensity and Frequency | Duration | Target Tissues or Animals | Main Finding | Reference |
---|---|---|---|---|---|
ELF-EMF | 3.1 mT (alternating magnetic field), 50 Hz | 18 h 1 session | H4 neuroglioma cells (H4/APPswe) | - ↑ total Aβ level 80% - ↑ Aβ42 level 32% | [71] |
100 μT (alternating magnetic field), 50 Hz | continuously 12 weeks | Sprague Dawley rats | - Insignificant change in Aβ level | [72] | |
VHF-EMF | 0.4 W/kg, 0.6 W/kg, 0.9 W/kg, 64 MHz | 1–2 h 4–14 days | Primary human brain (PHB) cells | - ↓ significantly in Aβ40 and Aβ42 levels | [73] |
RF-EMF | 0.20 W/kg, 918 MHz, 217 Hz pulse | 1 h 1 session | primary human and rat astrocytes | - ↓ ROS from Aβ42 and H2O2 - ↓ mitochondrial ROS formation induced by Aβ42 - ↓ activity of NADPH-oxidase by Aβ42 - ↑ mitochondrial membrane potential | [74] |
0.25–1.05 W/kg, 918 MHz, 217 Hz pulse | 2 h 12 days or 2 months | AβPPsw (Tg) mice | - ↓ Aβ burdens 30% in hippocampus and 24% in entorhinal cortex - ↑ significantly level of soluble Aβ1-40 in hippocampus and cortex | [75] | |
1.6 W/kg, 915 MHz | once or twice 1 h 2, 4, 12 months | 5 AD patents | - ↓ CSF levels of C-reactive protein, pTau217, Aβ40, and Aβ42 - modulating CSF oligomeric Aβ levels | [78] | |
5 W/kg, 1950 MHz | 2 h, 5 days per week 8 months | Tg-5xFAD mice | - ↓ ratio of Aβ42 and Aβ40 - ↓ APP and BACE1 expression - ↓ reduction of neuroinflammation | [76] | |
2 h, 5 days per week 3 months | - no affect in accumulation of Aβ - no affect in level of APP and CTFβ | [77] | |||
EMP | 50 kV/m, 100 Hz | 100, 1000, 10,000 pulses 2 months | Sprague Dawley rats | - ↑ Aβ protein level - ↑ expression of APP and Aβ oligomer | [68] |
- ↑ Aβ protein and oligomer - ↑ BACE1 and aberrant cleavage of APP | [69] |
Type of Infrared Light | Stimulation Intensity and Frequency | Duration | Target Tissues or Animals | Main Finding | Reference |
---|---|---|---|---|---|
Pulsed Infrared | 5 mW/cm2, 1072 nm pulse: 600 Hz (duty cycle 0.3 ms) | 6 min, two consecutive days biweekly for 5 months | Female TASTPM mice | - ↓ significantly in Aβ1-42 plaques in the cerebral cortex - ↓ αB-crystallin, APP, pTau, Aβ40 and Aβ42 (43–81%) protein expression - ↑ significantly in HSP60, 70 and 105 and phosphorylated-HSP27 | [82] |
Near infrared | 2 mW/cm2, 670 nm | 90 s, day, 5 days 4 consecutive weeks | APP/PS1 transgenic mouse and K3 mouse | - ↓ Aβ plaque burden in cerebellar cortex in APP/PS1 mice - ↓ formation of neurofibrillary tangles and hyperphosphorylation of tau - ↓ damage caused by oxidative stress | [84] |
30 mW/cm2, 808 nm | 5 min 1 session | Aβ treated microglia cells | - ↑ phagocytosis activated microglia level - ↓ inflammatory cytokines and extracellular ROS production - ↓ death of neurons caused by Aβ-altered microglia | [85] | |
Far infrared | 0.13 mW/cm2, 3000–25,000 nm | 1 h 1.5 months | APP/PS1 mice | - ↓ Aβ burden in cortex and hippocampus - ↓ neuroinflammation by activating microglia’s phagocytosis - ↑ ATP production and expression of the presynaptic protein synaptophysin - ↑ learning and memory ability | [87] |
Type of Ultrasound | Stimulation Intensity and Frequency | Duration | Subject | Main Finding | Reference | ||
---|---|---|---|---|---|---|---|
FUS | Type: LIPUS Frequency: 1 MHz Burst length: 50 ms PRF: 1 Hz Duty cycle: 5% | Sonication duration: 5 min with triple sonication daily for 42 daays | treated mice | - ↓ protein expression of Aβ content - ↓ memory retention and memory deficits - ↑ neurotrophic factors controlling or reversing AD | [108] | ||
Type: LIPUS Frequency: 1.875 MHz Burst length: 0.017 ms | Sonication duration: 20 min with triple sonication on days (1, 3, 5, 28, 30, 32, 56, 58, 60, 84) | 5XFAD mice | - ↓ Expression of APP and BACE-1, changes in characteristics of microglia and reduce Aβ - ↓ cognitive dysfunction by reducing Aβ and microgliosis | [109] | |||
Type: SUS Frequency: 1 MHz Acoustic pressure = 0.7 MPa Burst length: 10 ms PRF: 10 Hz Duty cycle: 10% | Sonication duration: 6 s per spot treated weakly for 5 weeks | APP23 mice | - insufficient in amyloid clearance - ↓ reductions in synaptic activity | [111] | |||
Type: LIPUS Frequency: 2 MHz Burst length: 0.4 ms PRF: 40 Hz Duty cycle: 5% | Sonication duration: 1 h single treatment/repeated treatment daily for 4 days | 5XFAD mice | - ↑ activation of microglia - ↓ reduction in Aβ burden | [110] | |||
FUS-MB | Type: MRIgFUS Frequency: 1.68 MHz Acoustic pressure: When sub-harmonic emissions were detected, the acoustic pressure was reduced to half and maintained for the remainder of sonication duration Burst length: 10 ms PRF: 1 Hz MB: Definity 0.02 mL/kg | Sonication duration: 120 s Weekly for 3 weeks | TgCRND8 mice | - ↓ significantly in Aβ - ↑ astrocytes and microglia which internalized amyloid - ↑ production of BDNF - ↑ Akt signaling | [118] | ||
Type: SUS Frequency: 1 MHz Acoustic pressure: 0.7 MPa Burst length: 10 ms PRF: 10 Hz Duty cycle: 10% MB: in-house Lipid-shelled MB 0.001 mL/g | Sonication duration: 6 s per spot Weekly for 6 or 7 weeks | APP23 mice | - ↑ microglia Aβ lysosomal activity - ↑ albumin entering the brain, which binds to Aβ and facilitates Aβ uptake by microglia - ↑ memory ability | [120] | |||
Type: Intracranial FUS Frequency: 1.1 MHz In situ pressure: 0.4–0.8 MPa Burst length: 10 ms PRF: 1 Hz MB: Definity 0.04 mL/kg | Type: MRIgFUS Frequency: 1.68 MHz Acoustic pressure: When sub-harmonic emissions reached threshold of 3.5 times the magnitude of background signals, the acoustic pressure was reduced by 50% and maintained for the remainder of sonication duration Burst length: 10 ms PRF: 1 Hz MB: Definity 0.02 mL/kg | Sonication duration: 120 s Single treatment | Sonication duration: 120 s Biweekly for 10 weeks | TgCRND8 mice | - ↑ infiltration of systemic phagocytic immune cells into the brain - ↑ phagocytosis of Aβ in microglia and astrocytes - ↑ entry of endogenous immunoglobulins which binds to Aβ plaque | [116] | |
Type: MRIgFUS Frequency: 220 kHz Acoustic pressure: When sub-harmonic emissions were detected, the acoustic pressure was reduced to half and maintained for the remainder of sonication duration Burst length: 2 ms on 28 ms off for 300 ms Repetition interval: 2.7 s MB: Definity 0.004 mL/kg | Sonication duration: 50 s Two treatment sessions with 1 month interval | Five 50–85 years old AD patients | - ↑ BBB open - no significant changes in cognition or functioning | [123] | |||
Type: FUS Frequency: 1.5 MHz Acoustic pressure: 0.45 MPa Burst length: 6.7 ms PRF: 10 Hz MB: in-house MB 0.0001 mL/g | Sonication duration: 60 s Weekly for 4 weeks | rTg4510 mice | - ↑ activation of microglia f infiltrating immune cells that help reduce pTau - ↑ migration of resident microglia - ↑ infiltration of peripheral immune cells through the BBB opening | [115] | |||
Type: SUS Frequency: 1 MHz Acoustic pressure: 0.25 MPa Burst length: 10 ms PRF: 1 Hz MB: Definity | Single treatment | K3691 tau transgenic mice | - ↓ active glial cells (microglia and astrocytes) - ↑ autophagy in neurons which contributes to tau clearance | [115] | |||
Type: FUS Frequency: 0.715 MHz Acoustic pressure: 0.42 MPa Burst length: 20 ms PRF: 1 Hz Duty cycle: 2% MB: SonoVue 0.1 mL | Sonication duration: 60 s Weekly for 6 weeks | 5xFAD mice | - ↑ clearance of Aβ via glymphatic-lymphatic system - ↑ restoration of memory via glymphatic-lymphatic clearance of amyloid | [114] | |||
Type: MRIgFUS Frequency: 220 kHz MB: Definity | Three treatment sessions with 2 weeks interval | Six early AD patients | - ↑ BBB open - no significant changes in clinical aspect | [124] | |||
Type: implantable ultrasound device (SonoCloud-1) Frequency: 1 MHz Acoustic pressure: 0.9 MPa–1.03 MPa MB: SonoVue 0.1 mL/Kg | Sonication duration: 4 min Every 2 weeks for 3.5 months | 10 AD patients | - no significant effect in Aβ accumulation and cognitive recognition | [126] | |||
FUS-MB with drug delivery | Type: MRIgFUS Frequency: 0.558 MHz Acoustic pressure: 0.3 MPa Burst length: 10 ms PRF: 1 Hz MB: Definity 0.16 mL/Kg | Sonication duration: 120 s Single treatment | TgCRND8 mice | - ↑ entering of anti-Aβ antibody into the brain - ↓ Aβ plaque burden (size and total surface area) | [129] | ||
Type: MRIgFUS Frequency: 1 MHz Acoustic pressure: 0.8 MPa Burst length: 10 ms PRF: 1 Hz MB: SonoVue 0.05 mL/kg | Sonication duration: 20 s Single treatment 3 repeated sessions with 3 days respectively | 2% high cholesterol diet New Zealand White rabbits | - ↑ entering of anti-Aβ antibody into the brain - ↑ anti-Aβ antibody | [131] | |||
Type: SUS Frequency: 1 MHz Acoustic pressure: 0.7 MPa Burst length: 10 ms PRF: 10 Hz Duty cycle: 10% MB: in-house Lipid-shelled MB 0.03 mL | Sonication duration: 6 s per spot Weekly for 4 weeks | pR5 mice | - ↓ interaction between GSK-3β and tau, thereby tau phosphorylation is prevented - ↓ phosphorylated tau levels - ↑ RN2N delivery across the BBB | [133] | |||
Type: MRIgFUS Frequency: 0.5515 MHz Acoustic pressure: based on the analysis of MB signal recording during each burst Burst length: 10 ms PRF: 1 Hz MB: Definity 0.04 mL/Kg | Sonication duration: 120 s Single treatment | TgCRND8 mice | - ↑ entering of BAM-10 into the brain, inducing clearance of Aβ | [135] | |||
Type: MRIgFUS Frequency: 0.69 MHz Peak negative pressure: 0.67–0.8 MPa Burst length: 10 ms PRF: 1 Hz | Sonication duration: 40–45 s | B6C3-Tg mice | - ↑ entering endogenous IgG and anti- Aβ antibodies - ↑ Aβ plaque clearing | [127] | |||
Type: FUS Frequency: 0.4 MHz Acoustic pressure: 0.41–0.5 MPa Burst length: 10 ms PRF: 1 Hz MB: SonoVue 0.01 mL/kg | Sonication duration: 60 s Single treatment 7 days (Exposure for a total 5 times) | APPswe/PSEN1-dE9 mice | -↑ GSK-3 inhibitor (AR-A014418) - ↓ Aβ significantly | [134] | |||
Type: FUS Frequency: 1 MHz Acoustic pressure: 0.41–0.5 MPa | Sonication duration: 180 s Single treatment | APP/PS1 mice | - ↑ delivery of Nanoparticles (PX@OP@RVG) into the brain - ↓ Aβ plaque and phosphorylated tau | [137] | |||
Type: SUS Frequency: 1 MHz Acoustic pressure: 0.65 MPa (for whole brain) /0.6 MPa (for hippocampus) Burst length: 10 ms PRF: 10 Hz Duty cycle: 10% MB: in-house Lipid-shelled MB 0.04 mL | Sonication duration: 6 s per spot (for whole brain) 60 s (for hippocampus) | pR5 mice | - ↑ various formats delivery of anti-tau antibody | [136] | |||
Type: MRIgFUS Frequency: 1.68 MHz Acoustic pressure: when a 840 Hz sub-harmonic was detected, the pressure amplitude was dropped to 50% and maintained for the remainder of sonication duration Burst length: 10 ms PRF: 1 Hz MB: Definity 0.02 mL/Kg | Sonication duration: 120 s Single treatment | TgCRND8 mice | - ↑ delivery of recombinant adeno-associated virus mosaic serotype - Regulate transgene expression near Aβ plaque | [139] | |||
Type: FUS Frequency: 0.4 MHz Acoustic pressure: 0.41–0.5 MPa Burst length: 10 ms PRF: 1 Hz MB: poly (α-cyanoacrylate n-butyl acrylate)-based MB | Sonication duration: 600 s Repeated treatment for 5 weeks | APP/PS1 mice | - ↑ local BBB opening and cognitive levels - ↑ nanoparticle release of Qc@SNPs into the brain - ↓ Aβ content and neuron loss | [135] | |||
Type: MRIgFUS Frequency: 1.68 MHz Acoustic pressure: Controlled by a feedback controller and allowed for consistent BBB permeabilization Burst length: 10 ms PRF: 1 Hz MB: Definity 0.02 mL/Kg | Sonication duration: 120 s single treatment (bioavailability study)/ weekly treatment for two weeks (Efficacy study) | TgCRND8 mice | - ↓ proinflammatory TNF-α - ↑ efflux of Aβ from brain - ↑ efficacy of IVIg by reducing AD pathology - ↑ neurogenesis in hippocampus | [128] |
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Bok, J.; Ha, J.; Ahn, B.J.; Jang, Y. Disease-Modifying Effects of Non-Invasive Electroceuticals on β-Amyloid Plaques and Tau Tangles for Alzheimer’s Disease. Int. J. Mol. Sci. 2023, 24, 679. https://doi.org/10.3390/ijms24010679
Bok J, Ha J, Ahn BJ, Jang Y. Disease-Modifying Effects of Non-Invasive Electroceuticals on β-Amyloid Plaques and Tau Tangles for Alzheimer’s Disease. International Journal of Molecular Sciences. 2023; 24(1):679. https://doi.org/10.3390/ijms24010679
Chicago/Turabian StyleBok, Junsoo, Juchan Ha, Bum Ju Ahn, and Yongwoo Jang. 2023. "Disease-Modifying Effects of Non-Invasive Electroceuticals on β-Amyloid Plaques and Tau Tangles for Alzheimer’s Disease" International Journal of Molecular Sciences 24, no. 1: 679. https://doi.org/10.3390/ijms24010679
APA StyleBok, J., Ha, J., Ahn, B. J., & Jang, Y. (2023). Disease-Modifying Effects of Non-Invasive Electroceuticals on β-Amyloid Plaques and Tau Tangles for Alzheimer’s Disease. International Journal of Molecular Sciences, 24(1), 679. https://doi.org/10.3390/ijms24010679