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Neurobiology of Aging and Aging-Related Disorders

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: closed (31 May 2022) | Viewed by 22883

Special Issue Editors


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Guest Editor
Department of Veterinary Medicine and Animal Production, University of Naples Federico II, 80137 Naples, Italy
Interests: central nervous system; animal models; vertebrates; neuropeptides; neurohistology; brain aging
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Guest Editor
Department of Veterinary Medicine, University of Naples Federico II, 80137 Naples, Italy
Interests: anatomy; teleost fish; neuropeptides; central and peripheral nervous system; animal models
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Faculty of Medicine, Universidad de Murcia, 30120 Murcia, Spain
Interests: anatomy; ageing; psycobiology; animal models; motor control; gene therapy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Brain ageing is a complex process of all vertebrate organisms and is influenced by systemic, genetic, and environmental factors. In course of ageing, the brain undergoes general morpho-physiological changes that include shrinkage of brain mass and myelin, decline of synaptic connections, and decreased neurotransmitter release. These modifications are associated with cognitive decline in information processing speed, memory, reasoning, and executive function, in addition to decreased well-being and increased symptoms of low mood. Furthermore, ageing is one of the major contributing factors for neurodegenerations and other brain diseases. Much of what we know about the impact of ageing on brain comes from model organisms (either vertebrate and invertebrates), which have been instrumental to identify factors that cause and modulate the ageing process. In this collection, we aim to address various aspects of the neurobiology of ageing and ageing related disorders, including a) new experimental approaches to modulate the ageing process with consequences on brain morpho-physiology; b) the identification of genetic and environmental factors related to brain ageing; and c) new imaging techniques and bioinformatics approaches to detect changes in the brain during ageing.

Dr. Livia D’Angelo
Dr. Paolo de Girolamo
Prof. Dr. María Trinidad Herrero
Guest Editors

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Keywords

  • brain ageing
  • gerontology
  • animal models
  • neurodegeneration

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Related Special Issue

Published Papers (7 papers)

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Research

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12 pages, 3306 KiB  
Article
Central and Peripheral NPY Age-Related Regulation: A Comparative Analysis in Fish Translational Models
by Daniela Giaquinto, Elena De Felice, Chiara Attanasio, Antonio Palladino, Valentina Schiano, Ernesto Mollo, Carla Lucini, Paolo de Girolamo and Livia D’Angelo
Int. J. Mol. Sci. 2022, 23(7), 3839; https://doi.org/10.3390/ijms23073839 - 30 Mar 2022
Cited by 7 | Viewed by 2511
Abstract
NPY is among the most abundant neuropeptides in vertebrate brain and is primarily involved in the regulation of food intake. The NPY system is also associated with the aging process showing beneficial effects on neuronal survival via autophagy modulation. Here, we explore the [...] Read more.
NPY is among the most abundant neuropeptides in vertebrate brain and is primarily involved in the regulation of food intake. The NPY system is also associated with the aging process showing beneficial effects on neuronal survival via autophagy modulation. Here, we explore the age-related regulation of NPY in the brain and foregut of the shortest- and longest-lived fish species, Nothobranchius furzeri and Danio rerio, respectively. These two research models, despite some similarities, display profound biological differences making them attractive vertebrates to elucidate the mechanisms underlying the regulation of neuropeptide synthesis and function. It is noteworthy that in both fish species only Npya has been identified, while in the other teleosts two classes of NPY (Npya and Npyb) have been annotated. Our findings document that in both species: (i) NPY is centrally regulated; (ii) NPY levels increase in the brain during aging; (iii) NPY is localized in the enteroendocrine cells as well as in the myenteric plexus and drastically decreases in old animals. According to our data, the age-related regulation in the gut resembles that described in other vertebrate species while the increased levels in the brain offer the unique possibility to explore the role of NPY in model organisms to develop future experimental and translatable approaches. Full article
(This article belongs to the Special Issue Neurobiology of Aging and Aging-Related Disorders)
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20 pages, 6070 KiB  
Article
Neuronal Phenotype of col4a1 and col25a1: An Intriguing Hypothesis in Vertebrates Brain Aging
by Adele Leggieri, Chiara Attanasio, Antonio Palladino, Paolo de Girolamo, Carla Lucini and Livia D’Angelo
Int. J. Mol. Sci. 2022, 23(3), 1778; https://doi.org/10.3390/ijms23031778 - 4 Feb 2022
Cited by 4 | Viewed by 2720
Abstract
Collagens are the most abundant proteins in vertebrates and constitute the major components of the extracellular matrix. Collagens play an important and multifaceted role in the development and functioning of the nervous system and undergo structural remodeling and quantitative modifications during aging. Here, [...] Read more.
Collagens are the most abundant proteins in vertebrates and constitute the major components of the extracellular matrix. Collagens play an important and multifaceted role in the development and functioning of the nervous system and undergo structural remodeling and quantitative modifications during aging. Here, we investigated the age-dependent regulation of col4a1 and col25a1 in the brain of the short-lived vertebrate Nothobranchius furzeri, a powerful model organism for aging research due to its natural fast-aging process and further characterized typical hallmarks of brain aging in this species. We showed that col4a1 and col25a1 are relatively well conserved during vertebrate evolution, and their expression significantly increases in the brain of N. furzeri upon aging. Noteworthy, we report that both col4a1 and col25a1 are expressed in cells with a neuronal phenotype, unlike what has already been documented in mammalian brain, in which only col25a1 is considered a neuronal marker, whereas col4a1 seems to be expressed only in endothelial cells. Overall, our findings encourage further investigation on the role of col4a1 and col25a1 in the biology of the vertebrate brain as well as the onset of aging and neurodegenerative diseases. Full article
(This article belongs to the Special Issue Neurobiology of Aging and Aging-Related Disorders)
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13 pages, 6479 KiB  
Article
The Effect of Ethanol on Disassembly of Amyloid-β1-42 Pentamer Revealed by Atomic Force Microscopy and Gel Electrophoresis
by Atsuya Matsui, Jean-Pierre Bellier, Takeshi Kanai, Hiroki Satooka, Akio Nakanishi, Tsukasa Terada, Takafumi Ishibe, Yoshiaki Nakamura, Hiroyasu Taguchi, Nobuyasu Naruse and Yutaka Mera
Int. J. Mol. Sci. 2022, 23(2), 889; https://doi.org/10.3390/ijms23020889 - 14 Jan 2022
Cited by 2 | Viewed by 2816
Abstract
The most common type of dementia, Alzheimer’s disease, is associated with senile plaques formed by the filamentous aggregation of hydrophobic amyloid-β (Aβ) in the brains of patients. Small oligomeric assemblies also occur and drugs and chemical compounds that can interact with such assemblies [...] Read more.
The most common type of dementia, Alzheimer’s disease, is associated with senile plaques formed by the filamentous aggregation of hydrophobic amyloid-β (Aβ) in the brains of patients. Small oligomeric assemblies also occur and drugs and chemical compounds that can interact with such assemblies have attracted much attention. However, these compounds need to be solubilized in appropriate solvents, such as ethanol, which may also destabilize their protein structures. As the impact of ethanol on oligomeric Aβ assembly is unknown, we investigated the effect of various concentrations of ethanol (0 to 7.2 M) on Aβ pentameric assemblies (Aβp) by combining blue native-PAGE (BN-PAGE) and ambient air atomic force microscopy (AFM). This approach was proven to be very convenient and reliable for the quantitative analysis of Aβ assembly. The Gaussian analysis of the height histogram obtained from the AFM images was correlated with band intensity on BN-PAGE for the quantitative estimation of Aβp. Our observations indicated up to 1.4 M (8.3%) of added ethanol can be used as a solvent/vehicle without quantitatively affecting Aβ pentamer stability. Higher concentration induced significant destabilization of Aβp and eventually resulted in the complete disassembly of Aβp. Full article
(This article belongs to the Special Issue Neurobiology of Aging and Aging-Related Disorders)
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14 pages, 3770 KiB  
Article
LC3/FtMt Colocalization Patterns Reveal the Progression of FtMt Accumulation in Nigral Neurons of Patients with Progressive Supranuclear Palsy
by Zulzikry Hafiz Abu Bakar, Jean-Pierre Bellier, Daijiro Yanagisawa, Tomoko Kato, Ken-ichi Mukaisho and Ikuo Tooyama
Int. J. Mol. Sci. 2022, 23(1), 537; https://doi.org/10.3390/ijms23010537 - 4 Jan 2022
Cited by 3 | Viewed by 2742
Abstract
Mitochondrial ferritin (FtMt) is a mitochondrial iron storage protein associated with neurodegenerative diseases. In patients with progressive supranuclear palsy (PSP), FtMt was shown to accumulate in nigral neurons. Here, we investigated FtMt and LC3 in the post-mortem midbrain of PSP patients to reveal [...] Read more.
Mitochondrial ferritin (FtMt) is a mitochondrial iron storage protein associated with neurodegenerative diseases. In patients with progressive supranuclear palsy (PSP), FtMt was shown to accumulate in nigral neurons. Here, we investigated FtMt and LC3 in the post-mortem midbrain of PSP patients to reveal novel aspects of the pathology. Immunohistochemistry was used to assess the distribution and abnormal changes in FtMt and LC3 immunoreactivities. Colocalization analysis using double immunofluorescence was performed, and subcellular patterns were examined using 3D imaging and modeling. In the substantia nigra pars compacta (SNc), strong FtMt-IR and LC3-IR were observed in the neurons of PSP patients. In other midbrain regions, such as the superior colliculus, the FtMt-IR and LC3-IR remained unchanged. In the SNc, nigral neurons were categorized into four patterns based on subcellular LC3/FtMt immunofluorescence intensities, degree of colocalization, and subcellular overlapping. This categorization suggested that concomitant accumulation of LC3/FtMt is related to mitophagy processes. Using the LC3-IR to stage neuronal damage, we retraced LC3/FtMt patterns and revealed the progression of FtMt accumulation in nigral neurons. Informed by these findings, we proposed a hypothesis to explain the function of FtMt during PSP progression. Full article
(This article belongs to the Special Issue Neurobiology of Aging and Aging-Related Disorders)
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17 pages, 5091 KiB  
Article
Amyloid-β Processing in Aged S100B Transgenic Mice Is Sex Dependent
by Krista Minéia Wartchow, Leticia Rodrigues, Izabela Swierzy, Michael Buchfelder, Diogo Onofre de Souza, Carlos-Alberto Gonçalves and Andrea Kleindienst
Int. J. Mol. Sci. 2021, 22(19), 10823; https://doi.org/10.3390/ijms221910823 - 6 Oct 2021
Cited by 6 | Viewed by 1944
Abstract
(1) Background: Calcium-binding protein S100B is involved in neuroregeneration but has also been associated with neurodegeneration. These contrasting effects may result from concentration or duration of exposure. We investigated the effect of long-term increased S100B levels on amyloid-β processing in one-year-old transgenic (tg) [...] Read more.
(1) Background: Calcium-binding protein S100B is involved in neuroregeneration but has also been associated with neurodegeneration. These contrasting effects may result from concentration or duration of exposure. We investigated the effect of long-term increased S100B levels on amyloid-β processing in one-year-old transgenic (tg) mice with 12 copies of the murine S100B gene with specific consideration of sex and specific brain regions. (2) Methods: S100B and amyloid-β 42 (Aβ42) were quantified in serum, cerebrospinal fluid (CSF), adipose tissue, and different brain regions by ELISA in wild-type (wt) and S100Btg mice (each n = 7 per group). Thioflavin T (ThT) and Aβ immunostaining were performed for visualization of Aβ deposition. (3) Results: S100B in serum, CSF, and brain was significantly increased in S100Btg mice of both sexes. Aβ42 was significantly increased in the hippocampus of male S100Btg mice (p = 0.0075), and the frontal cortex of female S100Btg mice (p = 0.0262). ThT and Aβ immunostaining demonstrated Aβ deposition in different brain regions in S100Btg mice of both sexes and female wt. (4) Conclusion: Our data validate this experimental model for studying the role of S100B in neurodegeneration and indicate that Aβ processing is sex-dependent and brain region-specific, which deserves further investigation of signaling pathways and behavioral responses. Full article
(This article belongs to the Special Issue Neurobiology of Aging and Aging-Related Disorders)
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14 pages, 9223 KiB  
Article
Localization of Neurotrophin Specific Trk Receptors in Mechanosensory Systems of Killifish (Nothobranchius guentheri)
by Marialuisa Aragona, Caterina Porcino, Maria Cristina Guerrera, Giuseppe Montalbano, Maria Levanti, Francesco Abbate, Rosaria Laurà and Antonino Germanà
Int. J. Mol. Sci. 2021, 22(19), 10411; https://doi.org/10.3390/ijms221910411 - 27 Sep 2021
Cited by 8 | Viewed by 2435
Abstract
Neurotrophins (NTs) and their signal-transducing Trk receptors play a crucial role in the development and maintenance of specific neuronal subpopulations in nervous and sensory systems. NTs are supposed to regulate two sensory systems in fish, the inner ear and the lateral line system [...] Read more.
Neurotrophins (NTs) and their signal-transducing Trk receptors play a crucial role in the development and maintenance of specific neuronal subpopulations in nervous and sensory systems. NTs are supposed to regulate two sensory systems in fish, the inner ear and the lateral line system (LLS). The latter is one of the major mechanosensory systems in fish. Considering that annual fishes of the genus Nothobranchius, with their short life expectancy, have become a suitable model for aging studies and that the occurrence and distribution of neurotrophin Trk receptors have never been investigated in the inner ear and LLS of killifish (Nothobranchius guentheri), our study aimed to investigate the localization of neurotrophin-specific Trk receptors in mechanosensory systems of N. guentheri. For histological and immunohistochemical analysis, adult specimens of N. guentheri were processed using antibodies against Trk receptors and S100 protein. An intense immunoreaction for TrkA and TrkC was found in the sensory cells of the inner ear as well as in the hair cells of LLS. Moreover, also the neurons localized in the acoustic ganglia displayed a specific immunoreaction for all Trk receptors (TrkA, B, and C) analyzed. Taken together, our results demonstrate, for the first time, that neurotrophins and their specific receptors could play a pivotal role in the biology of the sensory cells of the inner ear and LLS of N. guentheri and might also be involved in the hair cells regeneration process in normal and aged conditions. Full article
(This article belongs to the Special Issue Neurobiology of Aging and Aging-Related Disorders)
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Review

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20 pages, 2035 KiB  
Review
Cardiac Changes in Parkinson’s Disease: Lessons from Clinical and Experimental Evidence
by Lorena Cuenca-Bermejo, Pilar Almela, Javier Navarro-Zaragoza, Emiliano Fernández Villalba, Ana-María González-Cuello, María-Luisa Laorden and María-Trinidad Herrero
Int. J. Mol. Sci. 2021, 22(24), 13488; https://doi.org/10.3390/ijms222413488 - 16 Dec 2021
Cited by 20 | Viewed by 6029
Abstract
Dysautonomia is a common non-motor symptom in Parkinson’s disease (PD). Most dysautonomic symptoms appear due to alterations in the peripheral nerves of the autonomic nervous system, including both the sympathetic and parasympathetic nervous systems. The degeneration of sympathetic nerve fibers and neurons leads [...] Read more.
Dysautonomia is a common non-motor symptom in Parkinson’s disease (PD). Most dysautonomic symptoms appear due to alterations in the peripheral nerves of the autonomic nervous system, including both the sympathetic and parasympathetic nervous systems. The degeneration of sympathetic nerve fibers and neurons leads to cardiovascular dysfunction, which is highly prevalent in PD patients. Cardiac alterations such as orthostatic hypotension, heart rate variability, modifications in cardiogram parameters and baroreflex dysfunction can appear in both the early and late stages of PD, worsening as the disease progresses. In PD patients it is generally found that parasympathetic activity is decreased, while sympathetic activity is increased. This situation gives rise to an imbalance of both tonicities which might, in turn, promote a higher risk of cardiac damage through tachycardia and vasoconstriction. Cardiovascular abnormalities can also appear as a side effect of PD treatment: L-DOPA can decrease blood pressure and aggravate orthostatic hypotension as a result of a negative inotropic effect on the heart. This unwanted side effect limits the therapeutic use of L-DOPA in geriatric patients with PD and can contribute to the number of hospital admissions. Therefore, it is essential to define the cardiac features related to PD for the monitorization of the heart condition in parkinsonian individuals. This information can allow the application of intervention strategies to improve the course of the disease and the proposition of new alternatives for its treatment to eliminate or reverse the motor and non-motor symptoms, especially in geriatric patients. Full article
(This article belongs to the Special Issue Neurobiology of Aging and Aging-Related Disorders)
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