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20 pages, 9994 KiB

Open AccessArticle

Localization of Thioredoxin-Interacting Protein in Aging and Alzheimer’s Disease Brains

by Haruka Tsubaki, Anarmaa Mendsaikhan, Undral Buyandelger, Ikuo Tooyama and Douglas G. Walker

NeuroSci 2022, 3(2), 166-185; https://doi.org/10.3390/neurosci3020013 - 31 Mar 2022

Viewed by 3050

Abstract

Thioredoxin-Interacting Protein (TXNIP) has been shown to have significant pathogenic roles in many human diseases, particularly those associated with diabetes and hyperglycemia. Its main mode of action is to sequester thioredoxins, resulting in enhanced oxidative stress. The aim of this study was to [...] Read more.

Thioredoxin-Interacting Protein (TXNIP) has been shown to have significant pathogenic roles in many human diseases, particularly those associated with diabetes and hyperglycemia. Its main mode of action is to sequester thioredoxins, resulting in enhanced oxidative stress. The aim of this study was to identify if cellular expression of TXNIP in human aged and Alzheimer’s disease (AD) brains correlated with pathological structures. This study employed fixed tissue sections and protein extracts of temporal cortex from AD and aged control brains. Studies employed light and fluorescent immunohistochemical techniques using the monoclonal antibody JY2 to TXNIP to identify cellular structures. Immunoblots were used to quantify relative amounts of TXNIP in brain protein extracts. The major finding was the identification of TXNIP immunoreactivity in selective neuronal populations and structures, particularly in non-AD brains. In AD brains, less neuronal TXNIP but increased numbers of TXNIP-positive plaque-associated microglia were observed. Immunoblot analyses showed no significant increase in levels of TXNIP protein in the AD samples tested. In conclusion, this study identified altered patterns of expression of TXNIP in human brains with progression of AD pathology. Full article

(This article belongs to the Special Issue Feature Papers in Neurosci 2021)

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11 pages, 1360 KiB

Open AccessArticle

Neurocognitive Profiles of Caucasian Moyamoya Disease Patients in Greece: A Case Series

by Georgios Papageorgiou, Dimitrios Kasselimis, Georgia Angelopoulou, Dimitrios Tsolakopoulos, Nikolaos Laskaris, Argyro Tountopoulou, Eleni Korompoki, Georgios Velonakis, Achilles Chatziioannou, Konstantinos Spengos, Constantin Potagas and Sophia Vassilopoulou

NeuroSci 2022, 3(1), 119-129; https://doi.org/10.3390/neurosci3010010 - 23 Feb 2022

Cited by 1 | Viewed by 2769

Abstract

The impact of Moyamoya Disease (MMD) on cognition inadult Caucasian patients has not yet been thoroughly investigated. The current study is the first to present detailed neuropsychological data on a series of Greek patients with MMD. A group of eight patients was assessed [...] Read more.

The impact of Moyamoya Disease (MMD) on cognition inadult Caucasian patients has not yet been thoroughly investigated. The current study is the first to present detailed neuropsychological data on a series of Greek patients with MMD. A group of eight patients was assessed with an extensive neuropsychological battery, including measures of episodic memory, working memory, executive functions, language, and social cognition. The results indicated that MMD may be characterized by a trichotomous neurocognitive profile, characterized by prominent impairment in working memory, executive functions, and social cognition. Overall, we stress the need for a thorough cognitive evaluation of MMD patients and further highlight the potential importance of social cognition in this particular disease. Possible associations between the three impaired cognitive domains in our group are also discussed. Full article

(This article belongs to the Special Issue Feature Papers in Neurosci 2021)

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11 pages, 1657 KiB

Open AccessArticle

Transmembrane 29 (Tmem29), a Newly Identified Molecule Showed Downregulation in Hypoxic-Ischemic Brain Damage

by Hing-Wai Tsang, Inderjeet Bhatia, Koon-Wing Chan, Godfrey Chi-Fung Chan, Patrick Ip and Pik-To Cheung

NeuroSci 2022, 3(1), 41-51; https://doi.org/10.3390/neurosci3010003 - 1 Jan 2022

Cited by 1 | Viewed by 2840

Abstract

Transmembrane 29 (Tmem29) gene with unknown function is a gene located on the X chromosome of the mouse genome. The gene showed differential expression in the Vannucci neonatal hypoxic-ischemic mouse brain model. We found the gene expresses with different molecular forms, [...] Read more.

Transmembrane 29 (Tmem29) gene with unknown function is a gene located on the X chromosome of the mouse genome. The gene showed differential expression in the Vannucci neonatal hypoxic-ischemic mouse brain model. We found the gene expresses with different molecular forms, including a group of long non-coding RNA forming a family of transcripts. It was predominantly expressed in the testes, brain, and kidney of mouse. In vitro identification and functional characterization were carried out in Neuro2a cells. Using fluorescence microscopy, Tmem29 protein was found to be constitutively expressed in mouse cell lines of different origins. Oxygen glucose deprivation (OGD) induced apoptotic cell death in Neuro2a cells and was confirmed by activations of caspase 3. Tmem29 protein was found to be associated with cell death especially at the time points of caspase 3 activations. A similar response was obtained in glucose deprivation (GD) cultures suggesting Tmem29 response to a common mechanism induced by OGD and GD. Downregulation of Tmem29 was induced by OGD and GD, further validating its response to hypoxia-ischemia (HI) insults. Our findings contributed to further understanding of molecular events after hypoxic-ischemic insults and opens new avenues for developing protective and therapeutic strategies for hypoxic-ischemic encephalopathy or even pathological programmed cell death. Full article

(This article belongs to the Special Issue Feature Papers in Neurosci 2021)

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16 pages, 2542 KiB

Open AccessArticle

Predicting Fluid Intelligence via Naturalistic Functional Connectivity Using Weighted Ensemble Model and Network Analysis

by Xiaobo Liu, Su Yang and Zhengxian Liu

NeuroSci 2021, 2(4), 427-442; https://doi.org/10.3390/neurosci2040032 - 17 Dec 2021

Cited by 1 | Viewed by 2984

Abstract

Objectives: Functional connectivity triggered by naturalistic stimuli (e.g., movie clips), coupled with machine learning techniques provide great insight in exploring brain functions such as fluid intelligence. However, functional connectivity is multi-layered while traditional machine learning is based on individual model, which is not [...] Read more.

Objectives: Functional connectivity triggered by naturalistic stimuli (e.g., movie clips), coupled with machine learning techniques provide great insight in exploring brain functions such as fluid intelligence. However, functional connectivity is multi-layered while traditional machine learning is based on individual model, which is not only limited in performance, but also fails to extract multi-dimensional and multi-layered information from the brain network. Methods: In this study, inspired by multi-layer brain network structure, we propose a new method, namely weighted ensemble model and network analysis, which combines machine learning and graph theory for improved fluid intelligence prediction. Firstly, functional connectivity analysis and graphical theory were jointly employed. The functional connectivity and graphical indices computed using the preprocessed fMRI data were then all fed into an auto-encoder parallelly for automatic feature extraction to predict the fluid intelligence. In order to improve the performance, tree regression and ridge regression models were stacked and fused automatically with weighted values. Finally, layers of auto-encoder were visualized to better illustrate the connectome patterns, followed by the evaluation of the performance to justify the mechanism of brain functions. Results: Our proposed method achieved the best performance with a 3.85 mean absolute deviation, 0.66 correlation coefficient and 0.42 R-squared coefficient; this model outperformed other state-of-the-art methods. It is also worth noting that the optimization of the biological pattern extraction was automated though the auto-encoder algorithm. Conclusion: The proposed method outperforms the state-of-the-art reports, also is able to effectively capture the biological patterns of functional connectivity during a naturalistic movie state for potential clinical explorations. Full article

(This article belongs to the Special Issue Feature Papers in Neurosci 2021)

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17 pages, 4483 KiB

Open AccessArticle

The Influence of Burst-Firing EMF on Forskolin-Induced Pheochromocytoma (PC12) Plasma Membrane Extensions

by Trevor N. Carniello, Robert M. Lafrenie and Blake T. Dotta

NeuroSci 2021, 2(4), 383-399; https://doi.org/10.3390/neurosci2040028 - 6 Nov 2021

Cited by 1 | Viewed by 2735

Abstract

Previous research has demonstrated that pheochromocytoma (PC12) cells treated with forskolin provides a model for the in vitro examination of neuritogenesis. Exposure to electromagnetic fields (EMFs), especially those which have been designed to mimic biological function, can influence the functions of various biological [...] Read more.

Previous research has demonstrated that pheochromocytoma (PC12) cells treated with forskolin provides a model for the in vitro examination of neuritogenesis. Exposure to electromagnetic fields (EMFs), especially those which have been designed to mimic biological function, can influence the functions of various biological systems. We aimed to assess whether exposure of PC12 cells treated with forskolin to patterned EMF would produce more plasma membrane extensions (PME) as compared to PC12 cells treated with forskolin alone (i.e., no EMF exposure). In addition, we aimed to determine whether the differences observed between the proportion of PME of PC12 cells treated with forskolin and exposed to EMF were specific to the intensity, pattern, or timing of the applied EMF. Our results showed an overall increase in PME for PC12 cells treated with forskolin and exposed to Burst-firing EMF as compared to PC12 cells receiving forskolin alone. No other patterned EMF investigated were deemed to be effective. Furthermore, intensity and timing of the Burst-firing pattern did not significantly alter the proportion of PME of PC12 cells treated with forskolin and exposed to patterned EMF. Full article

(This article belongs to the Special Issue Feature Papers in Neurosci 2021)

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11 pages, 258 KiB

Open AccessCommunication

Developing the Concepts of Homeostasis, Homeorhesis, Allostasis, Elasticity, Flexibility and Plasticity of Brain Function

by Alfredo Pereira, Jr.

NeuroSci 2021, 2(4), 372-382; https://doi.org/10.3390/neurosci2040027 - 5 Nov 2021

Cited by 5 | Viewed by 5141

Abstract

I discuss some concepts advanced for the understanding of the complex dynamics of brain functions, and relate them to approaches in affective, cognitive and action neurosciences. These functions involve neuro-glial interactions in a dynamic system that receives sensory signals from the outside of [...] Read more.

I discuss some concepts advanced for the understanding of the complex dynamics of brain functions, and relate them to approaches in affective, cognitive and action neurosciences. These functions involve neuro-glial interactions in a dynamic system that receives sensory signals from the outside of the central nervous system, processes information in frequency, amplitude and phase-modulated electrochemical waves, and control muscles and glands to generate behavioral patterns. The astrocyte network is in charge of controlling global electrochemical homeostasis, and Hodgkin–Huxley dynamics drive the bioelectric homeostasis of single neurons. In elastic processes, perturbations cause instability, but the system returns to the basal equilibrium. In allostatic processes, perturbations elicit a response from the system, reacting to the deviation and driving the system to stable states far from the homeostatic equilibrium. When the system does not return to a fixed point or region of the state space, the process is called homeorhetic, and may present two types of evolution: (a) In flexible processes, there are previously existing “attractor” stable states that may be achieved after the perturbation, depending on context; (b) In plastic processes, the homeostatic set point(s) is(are) changed; the system is in a process of adaptation, in which the allostatic forces do not drive it back to the previous set point, but project to the new one. In the temporal phase from the deviant state to the recovery of stability, the system generates sensations that indicate if the recovery is successful (pleasure-like sensations) or if there is a failure (pain-like sensations). Full article

(This article belongs to the Special Issue Feature Papers in Neurosci 2021)

19 pages, 4067 KiB

Open AccessArticle

The Effect of Calcium Ions on Mechanosensation and Neuronal Activity in Proprioceptive Neurons

by Devan E. Atkins, Kimberly L. Bosh, Grace W. Breakfield, Sydney E. Daniels, Makayla J. Devore, Hailey E. Fite, Landys Z. Guo, Danielle K. J. Henry, Alana K. Kaffenberger, Katherine S. Manning, Tatum E. Mowery, Cecilia L. Pankau, Nyla Parker, Malina E. Serrano, Yamaan Shakhashiro, Hannah N. Tanner, Ruth. A. Ward, Aubrey. H. Wehry and Robin L. Cooper

NeuroSci 2021, 2(4), 353-371; https://doi.org/10.3390/neurosci2040026 - 22 Oct 2021

Cited by 9 | Viewed by 4431

Abstract

Proprioception of all animals is important in being able to have coordinated locomotion. Stretch activated ion channels (SACs) transduce the mechanical force into electrical signals in the proprioceptive sensory endings. The types of SACs vary among sensory neurons in animals as defined by [...] Read more.

Proprioception of all animals is important in being able to have coordinated locomotion. Stretch activated ion channels (SACs) transduce the mechanical force into electrical signals in the proprioceptive sensory endings. The types of SACs vary among sensory neurons in animals as defined by pharmacological, physiological and molecular identification. The chordotonal organs within insects and crustaceans offer a unique ability to investigate proprioceptive function. The effects of the extracellular environment on neuronal activity, as well as the function of associated SACs are easily accessible and viable in minimal saline for ease in experimentation. The effect of extracellular [Ca²⁺] on membrane properties which affect voltage-sensitivity of ion channels, threshold of action potentials and SACs can be readily addressed in the chordotonal organ in crab limbs. It is of interest to understand how low extracellular [Ca²⁺] enhances neural activity considering the SACs in the sensory endings could possibly be Ca²⁺ channels and that all neural activity is blocked with Mn2+. It is suggested that axonal excitability might be affected independent from the SAC activity due to potential presence of calcium activated potassium channels (K_(Ca)) and the ability of Ca²⁺ to block voltage gated Na⁺ channels in the axons. Separating the role of Ca²⁺ on the function of the SACs and the excitability of the axons in the nerves associated with chordotonal organs is addressed. These experiments may aid in understanding the mechanisms of neuronal hyperexcitability during hypocalcemia within mammals. Full article

(This article belongs to the Special Issue Feature Papers in Neurosci 2021)

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5 pages, 1029 KiB

Open AccessArticle

Optical Coherence Tomography to Monitor Rebound Intracranial Hypertension with Increased Papilledema after Lumbar Puncture

by Yumin Huang-Link, Pierfrancesco Mirabelli, Ge Yang, Andreas Eleftheriou and Hans Link

NeuroSci 2021, 2(4), 334-338; https://doi.org/10.3390/neurosci2040024 - 9 Oct 2021

Viewed by 3327

Abstract

Objective: We report that lumbar puncture (LP) with removal of cerebrospinal fluid (CSF) induced rebound intracranial hypertension with increased papilledema as monitored by optical coherence tomography (OCT). Background: Severe papilledema causes visual field loss and central vision damage if untreated. Fundoscopy is a [...] Read more.

Objective: We report that lumbar puncture (LP) with removal of cerebrospinal fluid (CSF) induced rebound intracranial hypertension with increased papilledema as monitored by optical coherence tomography (OCT). Background: Severe papilledema causes visual field loss and central vision damage if untreated. Fundoscopy is a key to diagnose papilledema, but is not sensitive enough to monitor therapeutic effects. Methods: OCT was applied to follow a 24-year-old woman with headache, visual dysfunction, severe bilateral papilledema, and elevated CSF opening pressure. She was first treated with serial LP, which led to symptom deterioration, increased CSF pressure, and increased the retinal nerve fiber layer (RNFL) thickness. She was then successfully treated with acetazolamide and furosemide. Results: OCT showed reduction of RNFL thickness directly after LP with CSF removal, accompanied with reduced CSF pressure. Increased RNFL thickness accompanied with worsened headache, visual dysfunction, and increased CSF pressure was observed on the next day after LP. Less than 24 h after start of medication, the symptoms had reversed and RNFL thickness was reduced. The patient was symptom-free 2 weeks after starting on medical treatment. Papilledema had vanished on fundoscopy 6 weeks after the therapy, and RNFL thickness was normalized at 3 months of follow-up. Conclusion: This case provides evidence that OCT is an objective and sensitive tool to monitor papilledema and its response to therapy, and thereby important to help in correct clinical decision-making. Full article

(This article belongs to the Special Issue Feature Papers in Neurosci 2021)

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14 pages, 1577 KiB

Open AccessArticle

A National Survey Evaluating the Impact of the COVID-19 Pandemic on Students Pursuing Careers in Neurosurgery

by Roxanna M. Garcia, Rebecca A. Reynolds, Hannah K. Weiss, Nathan A. Shlobin, Lola B. Chambless, Sandi Lam, Nader S. Dahdaleh and Gail Rosseau

NeuroSci 2021, 2(4), 320-333; https://doi.org/10.3390/neurosci2040023 - 3 Oct 2021

Cited by 6 | Viewed by 3111

Abstract

Background: The COVID-19 pandemic has profoundly disrupted medical education and the residency application process. Methods: We conducted a descriptive observational study in April 2020 of medical students and foreign medical graduates considering or pursuing careers in neurosurgery in the United States to examine [...] Read more.

Background: The COVID-19 pandemic has profoundly disrupted medical education and the residency application process. Methods: We conducted a descriptive observational study in April 2020 of medical students and foreign medical graduates considering or pursuing careers in neurosurgery in the United States to examine the impact of the pandemic. Results: A total of 379 respondents from 67 medical schools completed the survey. Across all participants, 92% (n = 347) stopped in-person didactic education, and 43% (n = 161) experienced basic science and 44% (n = 167) clinical research delays. Sixty percent (n = 227) cited a negative impact on academic productivity. Among first year students, 18% (n = 17) were less likely to pursue a career in neurosurgery. Over half of second year and third year students were likely to delay taking the United States Medical Licensing Examination Steps I and II. Among third year students, 77% (n = 91) reported indefinite postponement of sub-internships, and 43% (n = 53) were unsatisfied with communication from external programs. Many fourth-year students (50%, n = 17) were graduating early to participate in COVID-19-related patient care. Top student-requested support activities included access to student-focused educational webinars and sessions at upcoming conferences. Conclusions: Medical students pursuing careers in neurosurgery faced unique academic, career, and personal challenges secondary to the pandemic. These challenges may become opportunities for new initiatives guided by professional organizations and residency programs. Full article

(This article belongs to the Special Issue Feature Papers in Neurosci 2021)

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14 pages, 8658 KiB

Open AccessArticle

Knockout or Knock-in? A Truncated D2 Receptor Protein Is Expressed in the Brain of Functional D2 Receptor Knockout Mice

by Natalia Sánchez, Montserrat Olivares-Costa, Marcela P González, Roberto Munita, Angélica P Escobar, Rodrigo Meza, Mauricio Herrera-Rojas, Jessica Albornoz, Gianluca Merello and María E Andrés

NeuroSci 2021, 2(2), 193-206; https://doi.org/10.3390/neurosci2020014 - 1 Jun 2021

Cited by 1 | Viewed by 3784

Abstract

Null mice for the dopamine D2 receptor (D2R) have been instrumental in understanding the function of this protein. For our research, we obtained the functional D2R knockout mouse strain described initially in 1997. Surprisingly, our biochemical characterization showed that this mouse strain is [...] Read more.

Null mice for the dopamine D2 receptor (D2R) have been instrumental in understanding the function of this protein. For our research, we obtained the functional D2R knockout mouse strain described initially in 1997. Surprisingly, our biochemical characterization showed that this mouse strain is not a true knockout. We determined by sequence analysis of the rapid 3′ amplification of cDNA ends that functional D2R knockout mice express transcripts that lack only the eighth exon. Furthermore, immunofluorescence assays showed a D2R-like protein in the brain of functional D2R knockout mice. We verified by immunofluorescence that the recombinant truncated D2R is expressed in HEK293T cells, showing intracellular localization, colocalizing in the Golgi apparatus and the endoplasmic reticulum, but with less presence in the Golgi apparatus compared to the native D2R. As previously reported, functional D2R knockout mice are hypoactive and insensitive to the D2R agonist quinpirole. Concordantly, microdialysis studies confirmed that functional D2R knockout mice have lower extracellular dopamine levels in the striatum than the native mice. In conclusion, functional D2R knockout mice express transcripts that lead to a truncated D2R protein lacking from the sixth transmembrane domain to the C-terminus. We share these findings to avoid future confusion and the community considers this mouse strain in D2R traffic and protein–protein interaction studies. Full article

(This article belongs to the Special Issue Feature Papers in Neurosci 2021)

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11 pages, 2779 KiB

Open AccessArticle

Alcohol Consumption during Adulthood Does Not Impair Later Go/No-Go Reversal Learning in Male Rats

by Charles L. Pickens, Mark Gallo, Hayley Fisher, Alisa Pajser and Madelyn H. Ray

NeuroSci 2021, 2(2), 166-176; https://doi.org/10.3390/neurosci2020012 - 13 May 2021

Viewed by 3078

Abstract

Reversal learning tasks are used to model flexible decision-making in laboratory animals, and exposure to drugs of abuse can cause long-term impairments in reversal learning. However, the long-term effects of alcohol on reversal learning have varied. We evaluated whether six weeks of voluntary [...] Read more.

Reversal learning tasks are used to model flexible decision-making in laboratory animals, and exposure to drugs of abuse can cause long-term impairments in reversal learning. However, the long-term effects of alcohol on reversal learning have varied. We evaluated whether six weeks of voluntary alcohol consumption through chronic intermittent alcohol access (elevated by food restriction) in adult male rats would impair rats in a go/no-go reversal learning task when tested at an interval beyond acute withdrawal. In our go/no-go task, rats were reinforced for pressing one lever or withholding from pressing another lever, and the identities of the two levers were switched twice (once rats reached an accuracy criterion). We found no evidence that prior alcohol consumption altered discrimination or reversal learning in our task. This replicates previous patterns from our laboratory that higher alcohol consumption in food-restricted rats did not impair discrimination or reversal learning in a different go/no-go task and that alcohol consumption in free-fed adolescent/early adult rats did not impair go/no-go discrimination or reversal learning in the same task. It is unclear whether this represents an insensitivity of this task to alcohol exposure generally or whether an alcohol exposure procedure that leads to higher blood ethanol concentration (BEC) levels would impair learning. More research is needed to investigate these possibilities. Full article

(This article belongs to the Special Issue Feature Papers in Neurosci 2021)

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Review

Jump to: Research, Other

20 pages, 1125 KiB

Open AccessFeature PaperReview

The Relevance of Circadian Clocks to Stem Cell Differentiation and Cancer Progression

by Astha Malik, Shreya Nalluri, Arpan De, Dilshan Beligala and Michael E. Geusz

NeuroSci 2022, 3(2), 146-165; https://doi.org/10.3390/neurosci3020012 - 29 Mar 2022

Cited by 4 | Viewed by 4294

Abstract

The molecular mechanism of circadian clocks depends on transcription-translation feedback loops (TTFLs) that have known effects on key cellular processes. However, the distinct role of circadian TTFLs in mammalian stem cells and other less differentiated cells remains poorly understood. Neural stem cells (NSCs) [...] Read more.

The molecular mechanism of circadian clocks depends on transcription-translation feedback loops (TTFLs) that have known effects on key cellular processes. However, the distinct role of circadian TTFLs in mammalian stem cells and other less differentiated cells remains poorly understood. Neural stem cells (NSCs) of the brain generate neurons and glia postnatally but also may become cancer stem cells (CSCs), particularly in astrocytomas. Evidence indicates clock TTFL impairment is needed for tumor growth and progression; although, this issue has been examined primarily in more differentiated cancer cells rather than CSCs. Similarly, few studies have examined circadian rhythms in NSCs. After decades of research, it is now well recognized that tumors consist of CSCs and a range of other cancer cells along with noncancerous stromal cells. The circadian properties of these many contributors to tumor properties and treatment outcome are being widely explored. New molecular tools and ones in development will likely enable greater discrimination of important circadian and non-circadian cells within malignancies at multiple stages of cancer progression and following therapy. Here, we focus on adult NSCs and glioma CSCs to address how cells at different stages of differentiation may harbor unique states of the molecular circadian clock influencing differentiation and cell fate. Full article

(This article belongs to the Special Issue Feature Papers in Neurosci 2021)

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27 pages, 1172 KiB

Open AccessReview

Blood-Spinal Cord Barrier: Its Role in Spinal Disorders and Emerging Therapeutic Strategies

by Neha Chopra, Spiro Menounos, Jaesung P. Choi, Philip M. Hansbro, Ashish D. Diwan and Abhirup Das

NeuroSci 2022, 3(1), 1-27; https://doi.org/10.3390/neurosci3010001 - 21 Dec 2021

Cited by 9 | Viewed by 8857

Abstract

The blood-spinal cord barrier (BSCB) has been long thought of as a functional equivalent to the blood-brain barrier (BBB), restricting blood flow into the spinal cord. The spinal cord is supported by various disc tissues that provide agility and has different local immune [...] Read more.

The blood-spinal cord barrier (BSCB) has been long thought of as a functional equivalent to the blood-brain barrier (BBB), restricting blood flow into the spinal cord. The spinal cord is supported by various disc tissues that provide agility and has different local immune responses compared to the brain. Though physiologically, structural components of the BSCB and BBB share many similarities, the clinical landscape significantly differs. Thus, it is crucial to understand the composition of BSCB and also to establish the cause–effect relationship with aberrations and spinal cord dysfunctions. Here, we provide a descriptive analysis of the anatomy, current techniques to assess the impairment of BSCB, associated risk factors and impact of spinal disorders such as spinal cord injury (SCI), amyotrophic lateral sclerosis (ALS), peripheral nerve injury (PNI), ischemia reperfusion injury (IRI), degenerative cervical myelopathy (DCM), multiple sclerosis (MS), spinal cavernous malformations (SCM) and cancer on BSCB dysfunction. Along with diagnostic and mechanistic analyses, we also provide an up-to-date account of available therapeutic options for BSCB repair. We emphasize the need to address BSCB as an individual entity and direct future research towards it. Full article

(This article belongs to the Special Issue Feature Papers in Neurosci 2021)

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24 pages, 18234 KiB

Open AccessReview

GSK3β Activity in Reward Circuit Functioning and Addiction

by Jakub Turlik, Ewa Wąsikiewicz, Aleksandra Domaradzka, Gabriela Chrostek, Weronika Gniadzik, Mikołaj Domagalski and Przemysław Duda

NeuroSci 2021, 2(4), 443-466; https://doi.org/10.3390/neurosci2040033 - 17 Dec 2021

Cited by 2 | Viewed by 6896

Abstract

Glycogen synthase kinase-3β (GSK3β), primarily described as a regulator of glycogen metabolism, is a molecular hub linking numerous signaling pathways and regulates many cellular processes like cytoskeletal rearrangement, cell migration, apoptosis, and proliferation. In neurons, the kinase is engaged in molecular events related [...] Read more.

Glycogen synthase kinase-3β (GSK3β), primarily described as a regulator of glycogen metabolism, is a molecular hub linking numerous signaling pathways and regulates many cellular processes like cytoskeletal rearrangement, cell migration, apoptosis, and proliferation. In neurons, the kinase is engaged in molecular events related to the strengthening and weakening of synapses, which is a subcellular manifestation of neuroplasticity. Dysregulation of GSK3β activity has been reported in many neuropsychiatric conditions, like schizophrenia, major depressive disorder, bipolar disorder, and Alzheimer’s disease. In this review, we describe the kinase action in reward circuit-related structures in health and disease. The effect of pharmaceuticals used in the treatment of addiction in the context of GSK3β activity is also discussed. Full article

(This article belongs to the Special Issue Feature Papers in Neurosci 2021)

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11 pages, 2838 KiB

Open AccessFeature PaperReview

Status Epilepticus and Neurosyphilis: A Case Report and a Narrative Review

by Giada Giovannini and Stefano Meletti

NeuroSci 2021, 2(4), 416-426; https://doi.org/10.3390/neurosci2040031 - 1 Dec 2021

Viewed by 4589

Abstract

Neurosyphilis is a rare but life-threatening complication of syphilis that can develop even decades after the primary infection and can be unrecognized. Seizures and status epilepticus (SE) may represent the first manifestation in a previously undiagnosed syphilitic patient. We present an exemplification case [...] Read more.

Neurosyphilis is a rare but life-threatening complication of syphilis that can develop even decades after the primary infection and can be unrecognized. Seizures and status epilepticus (SE) may represent the first manifestation in a previously undiagnosed syphilitic patient. We present an exemplification case of a new onset refractory status epilepticus caused by neurosyphilis and we reviewed the existing literature. We selected all studies reporting cases of SE in the context both of patients with a known diagnosis of syphilis and as the first manifestation of neurosyphilis. We identified 50 patients, mostly composed of immunocompetent, middle-aged males. Thirty-nine patients (83%) presented a new onset SE. A history of subtle and rapidly progressive mood and/or cognitive impairment suggesting a limbic encephalitis-like presentation was frequently observed. Focal frontal or temporal SE was reported in 26. Brain MRI frequently showed T2/FLAIR hyperintensities widely involving the medial temporal structures and the frontal lobes. This review should increase the clinician’s awareness of neurosyphilis as a possible etiology of a new onset SE of unknown etiology, especially in the context of a “limbic encephalitis”-like clinical presentation. Prompt recognition and treatment for neurosyphilis partially or completely reverse neurologic sequelae, changing the natural history of the disease. Full article

(This article belongs to the Special Issue Feature Papers in Neurosci 2021)

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15 pages, 2629 KiB

Open AccessFeature PaperReview

Neuroprotective Effects of Resveratrol in Ischemic Brain Injury

by Noelia D. Machado, Gorka Villena Armas, Mariana A. Fernández, Santiago Grijalvo and David Díaz Díaz

NeuroSci 2021, 2(3), 305-319; https://doi.org/10.3390/neurosci2030022 - 1 Sep 2021

Cited by 7 | Viewed by 4576

Abstract

Cerebral ischemia represents the third cause of death and the first cause of disability in adults. This process results from decreasing cerebral blood flow levels as a result of the occlusion of a major cerebral artery. This restriction in blood supply generates low [...] Read more.

Cerebral ischemia represents the third cause of death and the first cause of disability in adults. This process results from decreasing cerebral blood flow levels as a result of the occlusion of a major cerebral artery. This restriction in blood supply generates low levels of oxygen and glucose, which leads to a decrease in the energy metabolism of the cell, producing inflammation, and finally, neurological deterioration. Currently, blood restoration of flow is the only effective approach as a therapy in terms of ischemic stroke. However, a significant number of patients still have a poor prognosis, probably owing to the increase in the generation of reactive oxygen species (ROS) during the reperfusion of damaged tissue. Oxidative stress and inflammation can be avoided by modulating mitochondrial function and have been identified as potential targets for the treatment of cerebral ischemia. In recent years, the beneficial actions of flavonoids and polyphenols against cerebrovascular diseases have been extensively investigated. The use of resveratrol (RSV) has been shown to markedly decrease brain damage caused by ischemia in numerous studies. According to in vitro and in vivo experiments, there is growing evidence that RSV is involved in several pathways, including cAMP/AMPK/SIRT1 regulation, JAK/ERK/STAT signaling pathway modulation, TLR4 signal transduction regulation, gut/brain axis modulation, GLUT3 up-regulation inhibition, neuronal autophagy activation, and de novo SUR1 expression inhibition. In this review, we summarize the recent outcomes based on the neuroprotective effect of RSV itself and RSV-loaded nanoparticles in vitro and in vivo models focusing on such mechanisms of action as well as describing the potential therapeutic strategies in which RSV plays an active role in cases of ischemic brain injury. Full article

(This article belongs to the Special Issue Feature Papers in Neurosci 2021)

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19 pages, 955 KiB

Open AccessReview

Fluoroquinolones-Associated Disability: It Is Not All in Your Head

by Maya Z. Freeman, Deanna N. Cannizzaro, Lydia F. Naughton and Cecilia Bove

NeuroSci 2021, 2(3), 235-253; https://doi.org/10.3390/neurosci2030017 - 16 Jul 2021

Cited by 13 | Viewed by 47785

Abstract

Fluoroquinolones (FQs) are a broad class of antibiotics typically prescribed for bacterial infections, including infections for which their use is discouraged. The FDA has proposed the existence of a permanent disability (Fluoroquinolone Associated Disability; FQAD), which is yet to be formally recognized. Previous [...] Read more.

Fluoroquinolones (FQs) are a broad class of antibiotics typically prescribed for bacterial infections, including infections for which their use is discouraged. The FDA has proposed the existence of a permanent disability (Fluoroquinolone Associated Disability; FQAD), which is yet to be formally recognized. Previous studies suggest that FQs act as selective GABA_A receptor inhibitors, preventing the binding of GABA in the central nervous system. GABA is a key regulator of the vagus nerve, involved in the control of gastrointestinal (GI) function. Indeed, GABA is released from the Nucleus of the Tractus Solitarius (NTS) to the Dorsal Motor Nucleus of the vagus (DMV) to tonically regulate vagal activity. The purpose of this review is to summarize the current knowledge on FQs in the context of the vagus nerve and examine how these drugs could lead to dysregulated signaling to the GI tract. Since there is sufficient evidence to suggest that GABA transmission is hindered by FQs, it is reasonable to postulate that the vagal circuit could be compromised at the NTS-DMV synapse after FQ use, possibly leading to the development of permanent GI disorders in FQAD. Full article

(This article belongs to the Special Issue Feature Papers in Neurosci 2021)

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15 pages, 986 KiB

Open AccessReview

A Critical Review of the Deviance Detection Theory of Mismatch Negativity

by Jamie A. O’Reilly and Amonrat O’Reilly

NeuroSci 2021, 2(2), 151-165; https://doi.org/10.3390/neurosci2020011 - 11 May 2021

Cited by 11 | Viewed by 4514

Abstract

Mismatch negativity (MMN) is a component of the difference waveform derived from passive auditory oddball stimulation. Since its inception in 1978, this has become one of the most popular event-related potential techniques, with over two-thousand published studies using this method. This is a [...] Read more.

Mismatch negativity (MMN) is a component of the difference waveform derived from passive auditory oddball stimulation. Since its inception in 1978, this has become one of the most popular event-related potential techniques, with over two-thousand published studies using this method. This is a testament to the ingenuity and commitment of generations of researchers engaging in basic, clinical and animal research. Despite this intensive effort, high-level descriptions of the mechanisms theorized to underpin mismatch negativity have scarcely changed over the past four decades. The prevailing deviance detection theory posits that MMN reflects inattentive detection of difference between repetitive standard and infrequent deviant stimuli due to a mismatch between the unexpected deviant and a memory representation of the standard. Evidence for these mechanisms is inconclusive, and a plausible alternative sensory processing theory considers fundamental principles of sensory neurophysiology to be the primary source of differences between standard and deviant responses evoked during passive oddball stimulation. By frequently being restated without appropriate methods to exclude alternatives, the potentially flawed deviance detection theory has remained largely dominant, which could lead some researchers and clinicians to assume its veracity implicitly. It is important to have a more comprehensive understanding of the source(s) of MMN generation before its widespread application as a clinical biomarker. This review evaluates issues of validity concerning the prevailing theoretical account of mismatch negativity and the passive auditory oddball paradigm, highlighting several limitations regarding its interpretation and clinical application. Full article

(This article belongs to the Special Issue Feature Papers in Neurosci 2021)

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8 pages, 779 KiB

Open AccessStudy Protocol

Effectiveness of Double-Hit Model (Post-Weaning Social Isolation and NMDA Receptor Antagonist) in the Development of Schizophrenic like Symptoms on Rodents: A Protocol for a Systematic Review

by Khanyiso Bright Shangase, Thabo Magwai, Fredrick Otieno Oginga, Khethelo Richman Xulu and Thabisile Mpofana

NeuroSci 2022, 3(1), 111-118; https://doi.org/10.3390/neurosci3010009 - 9 Feb 2022

Cited by 1 | Viewed by 2301

Abstract

Background: Schizophrenia is a heterogeneous neuropsychiatric disorder, categorized by positive, negative, and cognitive symptoms. In trying to improve the diagnosis and treatment of schizophrenia, researchers have turned to “dual hit” models of schizophrenia that are able to reproduce all symptoms of the disorder. [...] Read more.

Background: Schizophrenia is a heterogeneous neuropsychiatric disorder, categorized by positive, negative, and cognitive symptoms. In trying to improve the diagnosis and treatment of schizophrenia, researchers have turned to “dual hit” models of schizophrenia that are able to reproduce all symptoms of the disorder. The main objective of this protocol is to present a transparent process on how we plan to review the existing international literature on the effectiveness of “dual hit” models used to induce schizophrenia on rodents. Methods: Literature search strategies will be developed using medical search headings (MeSH). The MEDLINE (PubMed), EMBASE, and Google Scholar databases will be used to search for electronically published studies. We will search for studies involving inducing schizophrenic symptoms using “dual hit” rodent models (post-weaning social isolation and NMDA receptor antagonist). Studies will be screened by titles, abstracts, keywords, and synonyms followed by identifying the full-text articles. All studies that will pass quality assessment will be included. Data will be extracted by two authors independently and in duplicate from each eligible study to ensure that there is consistency between reviews. If the design and comparator are sufficiently homogenous for all studies, a meta-analysis will be conducted using a random-effect model. Discussion: The results of this review will contribute to the development of new “dual hit” models that will be able to characterize schizophrenia symptoms better. It will also shed light to researchers on new developments that need to be made in improving animal models of schizophrenia. Full article

(This article belongs to the Special Issue Feature Papers in Neurosci 2021)

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7 pages, 225 KiB

Open AccessProtocol

Early Life Stress and Brain Plasticity: From Alterations of Brain Morphology to Development of Psychopathology

by Fredrick Otieno Oginga, Thabo Magwai, Khanyiso Bright Shangase, Khethelo Richman Xulu and Thabisile Mpofana

NeuroSci 2022, 3(1), 104-110; https://doi.org/10.3390/neurosci3010008 - 3 Feb 2022

Cited by 3 | Viewed by 4810

Abstract

Advances in our understanding of the genetics of mental disorders (MD) have contributed to a better understanding of their pathophysiology. Nonetheless, several questions and doubts remain. Recent research has focused on the role of the environment in developing mental disorders, and the advent [...] Read more.

Advances in our understanding of the genetics of mental disorders (MD) have contributed to a better understanding of their pathophysiology. Nonetheless, several questions and doubts remain. Recent research has focused on the role of the environment in developing mental disorders, and the advent of neuroscientific methodologies has opened up new avenues of inquiry. However, the mechanism by which childhood stress affects neurodevelopment via mechanisms, such as gene-environment interactions and epigenetic regulation leading to diseases in adulthood, is unclear. This paper aims to review the evidence on the role of early life stress and parental psychopathology in the pathophysiology and clinical expression of MD. Methodology: The study will conduct a comprehensive systematic review using medical search terms (MeSH). Electronic searches for published studies will be performed using the MEDLINE (PubMed), EMBASE, Scopus, PsychINFO, Web of Science, and Google Scholar databases. We will look for research on the neuroplasticity effects of early life stress on development and review articles that evaluate cognitive functions and the development of psychopathology and MD. Before identifying full-text articles, several studies will be filtered based on titles, abstracts, keywords, and synonyms. Publications to be included in the review will be assessed for quality and consistency before inclusion. Data will be extracted independently and duplicated by two authors from each eligible study to ensure consistency between reviews. All databases will be searched from inception until July 2021 and will be limited to human studies. The search will be limited only to publication in the English language and any publication that can be converted to English. Discussion and Conclusions: The findings of this review will meticulously articulate the effects of childhood adversity, such as ELS and parental psychopathology on cognitive development and neuroplasticity. Full article

(This article belongs to the Special Issue Feature Papers in Neurosci 2021)

11 pages, 492 KiB

Open AccessBrief Report

A Retrospective Study of the Effects of Traumatic Brain Injury on Auditory Function: From a Clinical Perspective

by Mira White, Fauve Duquette-Laplante, Benoît Jutras, Caryn Bursch and Amineh Koravand

NeuroSci 2022, 3(1), 52-62; https://doi.org/10.3390/neurosci3010004 - 14 Jan 2022

Cited by 4 | Viewed by 4048

Abstract

Purpose: The main purpose of this retrospective study was to identify auditory dysfunctions related to traumatic brain injury (TBI) in individuals evaluated in an Audiology clinic. Method: Peripheral and central auditory evaluations were performed from March 2014 to June 2018 in 26 patients [...] Read more.

Purpose: The main purpose of this retrospective study was to identify auditory dysfunctions related to traumatic brain injury (TBI) in individuals evaluated in an Audiology clinic. Method: Peripheral and central auditory evaluations were performed from March 2014 to June 2018 in 26 patients (14 males) with TBI. The age of the participants ranged from 9 to 59 years old (34.24 ± 15.21). Six participants had blast-related TBI and 20 had blunt force TBI. Sixteen experienced a single TBI event whereas ten experienced several. Correlation analyses were performed to verify the relationship, if any, between the number of auditory tests failed and the number, type, and severity of TBIs. Result: All participants failed at least one auditory test. Nearly 60% had abnormal results on degraded speech tests (compressed and echoed, filtered or in background noise) and 25% had a high frequency hearing loss. There was no statistically significant correlation between the number of auditory tests failed and the number, type, and severity of TBIs. Conclusion: Results indicated negative and heterogenous effects of TBI on peripheral and central auditory function and highlighted the need for a more extensive auditory assessment in individuals with TBI. Full article

(This article belongs to the Special Issue Feature Papers in Neurosci 2021)

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5 pages, 423 KiB

Open AccessCase Report

Repetitive Transcranial Magnetic Stimulation for Major Depressive Disorder Comorbid with Huntington’s Disease: A Case Report

by Clémence Noiseux, Jean-Philippe Miron, Véronique Desbeaumes Jodoin, Tian Ren Chu, Sylvain Chouinard and Paul Lespérance

NeuroSci 2021, 2(4), 400-404; https://doi.org/10.3390/neurosci2040029 - 25 Nov 2021

Cited by 1 | Viewed by 2845

Abstract

Huntington’s disease (HD) is a rare genetic disorder resulting in progressive neurodegeneration leading to motor, cognitive and psychiatric symptoms. A high percentage of HD patients suffer from comorbid major depressive disorder (MDD). We are not aware of any literature on the use of [...] Read more.

Huntington’s disease (HD) is a rare genetic disorder resulting in progressive neurodegeneration leading to motor, cognitive and psychiatric symptoms. A high percentage of HD patients suffer from comorbid major depressive disorder (MDD). We are not aware of any literature on the use of repetitive transcranial magnetic stimulation (rTMS) for treating comorbid MDD in HD. We present the case of a 57-year-old man suffering from HD in which comorbid MDD was successfully treated with rTMS. Further work is required to better characterize the safety, tolerability and effectiveness of rTMS to treat comorbid MDD in HD. Full article

(This article belongs to the Special Issue Feature Papers in Neurosci 2021)

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14 pages, 649 KiB

Open AccessSystematic Review

Facial Emotion Recognition in Obesity and in Fibromyalgia: A Systematic Review

by Giulia Vaioli and Federica Scarpina

NeuroSci 2021, 2(4), 339-352; https://doi.org/10.3390/neurosci2040025 - 12 Oct 2021

Cited by 6 | Viewed by 3184

Abstract

Facial emotion recognition (FER) is extensively investigated in psychological sciences in healthy individuals and clinical conditions. In this paper, we analyzed those studies in which FER was assessed in the case of obesity or fibromyalgia, in relation to the levels of alexithymia. Crucially, [...] Read more.

Facial emotion recognition (FER) is extensively investigated in psychological sciences in healthy individuals and clinical conditions. In this paper, we analyzed those studies in which FER was assessed in the case of obesity or fibromyalgia, in relation to the levels of alexithymia. Crucially, these two conditions frequently co-occur; however, no study has explored FER considering both fibromyalgia and obesity. Studies were identified using the electronic search engine of PubMed. The last research was run on 23 July 2021. Two independent lists were generated for the two clinical conditions. Six records were reviewed about obesity, while three records about fibromyalgia. The evidence relative to FER in obesity was not conclusive, whereas the evidence about an altered FER in fibromyalgia seemed more straightforward. Moreover, the role of alexithymia on FER in these clinical conditions was not extensively investigated. In our discussion, we highlighted those factors that should be carefully addressed in investigating FER in these clinical conditions. Moreover, we underlined methodological criticisms that should be overcome in future research. Full article

(This article belongs to the Special Issue Feature Papers in Neurosci 2021)

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6 pages, 653 KiB

Open AccessCase Report

Botulinum Toxin Treatment for Thoracic Outlet Syndrome Induced by Subclavius Muscle Hypertrophy

by Francesco Cavallieri, Stefano Galletti, Valentina Fioravanti, Elisa Menozzi, Sara Contardi and Franco Valzania

NeuroSci 2021, 2(2), 135-140; https://doi.org/10.3390/neurosci2020009 - 22 Apr 2021

Cited by 5 | Viewed by 7127

Abstract

Thoracic outlet syndrome (TOS) is frequently caused by bone abnormalities and congenital or acquired soft-tissue alterations. Among these, isolated Subclavius Muscle (SM) hypertrophy represents a rare condition that could lead to a reduction in costoclavicular space and brachial plexus compression. A 47-year-old forest [...] Read more.

Thoracic outlet syndrome (TOS) is frequently caused by bone abnormalities and congenital or acquired soft-tissue alterations. Among these, isolated Subclavius Muscle (SM) hypertrophy represents a rare condition that could lead to a reduction in costoclavicular space and brachial plexus compression. A 47-year-old forest ranger with a history of gun shooting during animal hunting and training sessions of skeet shooting for 20 years developed TOS due to ultrasonography-detected isolated SM hypertrophy, successfully treated with an ultrasound-guided Botulinum Toxin (BTX)-A injection. In our patient, ultrasonography of the brachial plexus has allowed SM hypertrophy to be recognized and to perform BTX-A injection just in the muscle, with a complete resolution of the symptoms. Full article

(This article belongs to the Special Issue Feature Papers in Neurosci 2021)

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15 pages, 1160 KiB

Open AccessPerspective

Pathophysiological Correlation between Cigarette Smoking and Amyotrophic Lateral Sclerosis

by Spiro Menounos, Philip M. Hansbro, Ashish D. Diwan and Abhirup Das

NeuroSci 2021, 2(2), 120-134; https://doi.org/10.3390/neurosci2020008 - 20 Apr 2021

Cited by 1 | Viewed by 4699

Abstract

Cigarette smoke (CS) has been consistently demonstrated to be an environmental risk factor for amyotrophic lateral sclerosis (ALS), although the molecular pathogenic mechanisms involved are yet to be elucidated. Here, we propose different mechanisms by which CS exposure can cause sporadic ALS pathogenesis. [...] Read more.

Cigarette smoke (CS) has been consistently demonstrated to be an environmental risk factor for amyotrophic lateral sclerosis (ALS), although the molecular pathogenic mechanisms involved are yet to be elucidated. Here, we propose different mechanisms by which CS exposure can cause sporadic ALS pathogenesis. Oxidative stress and neuroinflammation are widely implicated in ALS pathogenesis, with blood–spinal cord barrier disruption also recognised to be involved in the disease process. In addition, immunometabolic, epigenetic and microbiome alterations have been implicated in ALS recently. Identification of the underlying pathophysiological mechanisms that underpin CS-associated ALS will drive future research to be conducted into new targets for treatment. Full article

(This article belongs to the Special Issue Feature Papers in Neurosci 2021)

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