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https://www.readbyqxmd.com/read/28222529/progressive-motor-deficit-is-mediated-by-the-denervation-of-neuromuscular-junctions-and-axonal-degeneration-in-transgenic-mice-expressing-mutant-p301s-tau-protein
#1
Zhuoran Yin, Femke Valkenburg, Betty E Hornix, Ietje Mantingh-Otter, Xingdong Zhou, Muriel Mari, Fulvio Reggiori, Debby Van Dam, Bart J L Eggen, Peter P De Deyn, Erik Boddeke
Tauopathies include a variety of neurodegenerative diseases associated with the pathological aggregation of hyperphosphorylated tau, resulting in progressive cognitive decline and motor impairment. The underlying mechanism for motor deficits related to tauopathy is not yet fully understood. Here, we use a novel transgenic tau mouse line, Tau 58/4, with enhanced neuron-specific expression of P301S mutant tau to investigate the motor abnormalities in association with the peripheral nervous system. Using stationary beam, gait, and rotarod tests, motor deficits were found in Tau 58/4 mice already 3 months after birth, which deteriorated during aging...
February 10, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/28220607/neurological-and-spinal-manifestations-of-the-ehlers-danlos-syndromes
#2
Fraser C Henderson, Claudiu Austin, Edward Benzel, Paolo Bolognese, Richard Ellenbogen, Clair A Francomano, Candace Ireton, Petra Klinge, Myles Koby, Donlin Long, Sunil Patel, Eric L Singman, Nicol C Voermans
The Ehlers-Danlos syndromes (EDS) are a heterogeneous group of heritable connective tissue disorders characterized by joint hypermobility, skin extensibility, and tissue fragility. This communication briefly reports upon the neurological manifestations that arise including the weakness of the ligaments of the craniocervical junction and spine, early disc degeneration, and the weakness of the epineurium and perineurium surrounding peripheral nerves. Entrapment, deformation, and biophysical deformative stresses exerted upon the nervous system may alter gene expression, neuronal function and phenotypic expression...
February 21, 2017: American Journal of Medical Genetics. Part C, Seminars in Medical Genetics
https://www.readbyqxmd.com/read/28219641/neural-stem-cell-therapy-for-neurodegenerative-disorders-the-role-of-neurotrophic-support
#3
Samuel E Marsh, Mathew Blurton-Jones
Neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, and Huntington's disease currently affect tens of millions of people worldwide. Unfortunately, as the world's population ages, the incidence of many of these diseases will continue to rise and is expected to more than double by 2050. Despite significant research and a growing understanding of disease pathogenesis, only a handful of therapies are currently available and all of them provide only transient benefits. Thus, there is an urgent need to develop novel disease-modifying therapies to prevent the development or slow the progression of these debilitating disorders...
February 17, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28217083/postnatal-loss-of-neuronal-and-glial-neurofascins-differentially-affects-node-of-ranvier-maintenance-and-myelinated-axon-function
#4
Anna M Taylor, Julia Saifetiarova, Manzoor A Bhat
Intricate molecular interactions between neurons and glial cells underlie the creation of unique domains that are essential for saltatory conduction of action potentials by myelinated axons. Previously, the cell surface adhesion molecule Neurofascin (Nfasc) has been shown to have a dual-role in the establishment of axonal domains from both the glial and neuronal interface. While the neuron-specific isoform of Neurofascin (NF186) is indispensable for clustering of voltage-gated sodium channels at nodes of Ranvier; the glial-specific isoform of Neurofascin (NF155) is required for myelinating glial cells to organize the paranodal domain...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28216676/fractalkine-cx3cr1-signaling-is-critical-for-progesterone-mediated-neuroprotection-in-the-retina
#5
Sarah L Roche, Alice C Wyse-Jackson, Ana M Ruiz-Lopez, Ashleigh M Byrne, Thomas G Cotter
Retinitis pigmentosa (RP) encompasses a group of retinal diseases resulting in photoreceptor loss and blindness. We have previously shown in the rd10 mouse model of RP, that rd10 microglia drive degeneration of viable neurons. Norgestrel, a progesterone analogue, primes viable neurons against potential microglial damage. In the current study we wished to investigate this neuroprotective effect further. We were particularly interested in the role of fractalkine-CX3CR1 signaling, previously shown to mediate photoreceptor-microglia crosstalk and promote survival in the rd10 retina...
February 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28214917/mtss1-promotes-maturation-and-maintenance-of-cerebellar-neurons-via-splice-variant-specific-effects
#6
Thorsten Sistig, Fanziska Lang, Sebastian Wrobel, Stephan L Baader, Karl Schilling, Britta Eiberger
Efficient coupling of the actin cytoskeleton to the cell membrane is crucial for histogenesis and maintenance of the nervous system. At this critical interface, BAR (Bin-Amphiphysin-Rvs) proteins regulate membrane bending, shown to be instrumental for mobility and morphogenesis of individual cells. Yet, the systemic significance of these proteins remains largely unexplored. Here, we probe the role of a prominent member of this protein family, the inverse-BAR protein Mtss1, for the development and function of a paradigmatic neuronal circuit, the cerebellar cortex...
February 18, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/28213588/a-differential-autophagy-dependent-response-to-dna-double-strand-brakes-in-bone-marrow-mesenchymal-stem-cells-from-sporadic-als-patients
#7
Shane Wald-Altman, Edward Pichinuk, Or Kakhlon, Miguel Weil
Amyotrophic Lateral Sclerosis (ALS) is an incurable motor neurodegenerative disease caused by a diversity of genetic and environmental factors leading to neuromuscular degeneration and pathophysiological implications in non-neural systems. Our previous work showed abnormal transcriptional expression levels of biomarker genes in non-neuronal cell samples from ALS patients. The same genes proved to be differentially expressed in brain, spinal cord and muscle of the SOD1(G93A) ALS mouse model. These observations support the pathophysiological relevance of the ALS biomarkers discovered in human mesenchymal stem cells (hMSC) isolated from bone marrow samples of ALS patients (ALS-hMSC)...
February 16, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28213070/selective-a2a-receptors-blockade-reduces-degeneration-of-substantia-nigra-dopamine-neurons-in-a-rotenone-induced-rat-model-of-parkinson-s-disease-a-histological-study
#8
Ahmed M Fathalla, Amira M Soliman, Ahmed A Moustafa
Parkinson's disease (PD) is characterized by a loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). Adenosine is a neuromodulator that inhibit the release of dopamine via a disinhibitory mechanism. In this study, we investigated the neuroprotective effect of 8-cyclopentyl-1,3-dipropylxanthine and ZM241385 (respectively, A1 and A2A receptors antagonists), on nigrostriatal dopamine neurons degradation reduction in a rotenone-induced PD model using histopathological and immunohistochemical methods...
February 15, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28212893/traffic-related-air-pollution-impact-on-mouse-brain-accelerates-myelin-and-neuritic-aging-changes-with-specificity-for-ca1-neurons
#9
Nicholas C Woodward, Payam Pakbin, Arian Saffari, Farimah Shirmohammadi, Amin Haghani, Constantinos Sioutas, Mafalda Cacciottolo, Todd E Morgan, Caleb E Finch
Traffic-related air pollution (TRAP) is associated with lower cognition and reduced white matter volume in older adults, specifically for particulate matter <2.5-μm diameter (PM2.5). Rodents exposed to TRAP have shown microglial activation and neuronal atrophy. We further investigated age differences of TRAP exposure, with focus on hippocampus for neuritic atrophy, white matter degeneration, and microglial activation. Young- and middle-aged mice (3 and 18 months female C57BL/6J) were exposed to nanoscale-PM (nPM, <0...
January 13, 2017: Neurobiology of Aging
https://www.readbyqxmd.com/read/28212525/ablation-of-ferroptosis-regulator-glutathione-peroxidase-4-in-forebrain-neurons-promotes-cognitive-impairment-and-neurodegeneration
#10
William Sealy Hambright, Rene Solano Fonseca, Liuji Chen, Ren Na, Qitao Ran
Synaptic loss and neuron death are the underlying cause of neurodegenerative diseases such as Alzheimer's disease (AD); however, the modalities of cell death in those diseases remain unclear. Ferroptosis, a newly identified oxidative cell death mechanism triggered by massive lipid peroxidation, is implicated in the degeneration of neurons populations such as spinal motor neurons and midbrain neurons. Here, we investigated whether neurons in forebrain regions (cerebral cortex and hippocampus) that are severely afflicted in AD patients might be vulnerable to ferroptosis...
February 1, 2017: Redox Biology
https://www.readbyqxmd.com/read/28212107/rheb-in-neuronal-degeneration-regeneration-and-connectivity
#11
Veena Nambiar Potheraveedu, Miriam Schöpel, Raphael Stoll, Rolf Heumann
The small GTPase Rheb was originally detected as an immediate early response protein whose expression was induced by NMDA-dependent synaptic activity in the brain. Rheb's activity is highly regulated by its GTPase activating protein (GAP), the tuberous sclerosis complex protein, which stimulates the conversion from the active, GTP-loaded into the inactive, GDP-loaded conformation. Rheb has been established as an evolutionarily conserved molecular switch protein regulating cellular growth, cell volume, cell cycle, autophagy, and amino acid uptake...
February 17, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28211008/injected-amyloid-beta-in-the-olfactory-bulb-transfers-to-other-brain-regions-via-neural-connections-in-mice
#12
Baixuan He, Minying Zheng, Qiang Liu, Zhe Shi, Simei Long, Xilin Lu, Zhong Pei, Ti-Fei Yuan, Huanxing Su, Xiaoli Yao
Alzheimer's disease (AD) is characterized by progressive neuronal degeneration and pathological accumulation of amyloid plaques in the brain. It has been proposed that the prion-like spreading of amyloid beta (Aβ) protein could contribute to the progression of the disease. Olfactory bulb (OB) is one of the earliest brain regions affected in AD and olfaction is easily impaired prior to cognitive symptoms. However, it remains unclear whether Aβ accumulation in the OB would spread along olfactory projections to other connected brain regions and trigger further neurodegeneration...
February 16, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28210876/effect-of-hyperhomocysteinemia-on-redox-balance-and-redox-defence-enzymes-in-ischemia-reperfusion-injury-and-or-after-ischemic-preconditioning-in-rats
#13
Martin Petráš, Anna Drgová, Mária Kovalská, Zuzana Tatarková, Barbara Tóthová, Oľga Križanová, Ján Lehotský
Increased level of homocysteine (hHcy) in plasma is an accompanying phenomenon of many diseases, including a brain stroke. This study determines whether hyperhomocysteinemia (which is a risk factor of brain ischemia) itself or in combination with ischemic preconditioning affects the ischemia-induced neurodegenerative changes, generation of reactive oxygen species (ROS), lipoperoxidation, protein oxidation, and activity of antioxidant enzymes in the rat brain cortex. The hHcy was induced by subcutaneous administration of homocysteine (0...
February 16, 2017: Cellular and Molecular Neurobiology
https://www.readbyqxmd.com/read/28210207/cannabinoid-receptor-2-signaling-in-neurodegenerative-disorders-from-pathogenesis-to-a-promising-therapeutic-target
#14
REVIEW
Tommaso Cassano, Silvio Calcagnini, Lorenzo Pace, Federico De Marco, Adele Romano, Silvana Gaetani
As a consequence of an increasingly aging population, the number of people affected by neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease and Huntington's disease, is rapidly increasing. Although the etiology of these diseases has not been completely defined, common molecular mechanisms including neuroinflammation, excitotoxicity and mitochondrial dysfunction have been confirmed and can be targeted therapeutically. Moreover, recent studies have shown that endogenous cannabinoid signaling plays a number of modulatory roles throughout the central nervous system (CNS), including the neuroinflammation and neurogenesis...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28209901/vitamin-b3-modulates-mitochondrial-vulnerability-and-prevents-glaucoma-in-aged-mice
#15
Pete A Williams, Jeffrey M Harder, Nicole E Foxworth, Kelly E Cochran, Vivek M Philip, Vittorio Porciatti, Oliver Smithies, Simon W M John
Glaucomas are neurodegenerative diseases that cause vision loss, especially in the elderly. The mechanisms initiating glaucoma and driving neuronal vulnerability during normal aging are unknown. Studying glaucoma-prone mice, we show that mitochondrial abnormalities are an early driver of neuronal dysfunction, occurring before detectable degeneration. Retinal levels of nicotinamide adenine dinucleotide (NAD(+), a key molecule in energy and redox metabolism) decrease with age and render aging neurons vulnerable to disease-related insults...
February 17, 2017: Science
https://www.readbyqxmd.com/read/28209736/pejvakin-a-candidate-stereociliary-rootlet-protein-regulates-hair-cell-function-in-a-cell-autonomous-manner
#16
Marcin Kazmierczak, Piotr Kazmierczak, Anthony W Peng, Suzan L Harris, Prahar Shah, Jean-Luc Puel, Marc Lenoir, Santos J Franco, Martin Schwander
Mutations in the Pejvakin (PJVK) gene are thought to cause auditory neuropathy and hearing loss of cochlear origin by affecting noise-induced peroxisome proliferation in auditory hair cells and neurons. Here we demonstrate that loss of pejvakin in hair cells, but not in neurons, causes profound hearing loss and outer hair cell degeneration in mice. Pejvakin binds to and co-localizes with the rootlet component TRIOBP at the base of stereocilia in injectoporated hair cells, a pattern that is disrupted by deafness-associated PJVK mutations...
February 16, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28209643/eif2%C3%AE-links-mitochondrial-dysfunction-to-dendritic-degeneration
#17
Xin Qi
Although mitochondrial dysfunction has been associated with dendritic pathology in many neuronal types, how mitochondrial impairment causes the vulnerability of neuronal subtypes remains unknown. In this issue, Tsuyama et al. (2017. J. Cell Biol. https://doi.org/10.1083/jcb.201604065) identify eIF2α phosphorylation as a critical regulator of mitochondrial dysfunction-mediated selective dendritic loss in Drosophila neurons.
February 16, 2017: Journal of Cell Biology
https://www.readbyqxmd.com/read/28208742/aav-vector-mediated-gene-delivery-to-substantia-nigra-dopamine-neurons-implications-for-gene-therapy-and-disease-models
#18
REVIEW
Katrina Albert, Merja H Voutilainen, Andrii Domanskyi, Mikko Airavaara
Gene delivery using adeno-associated virus (AAV) vectors is a widely used method to transduce neurons in the brain, especially due to its safety, efficacy, and long-lasting expression. In addition, by varying AAV serotype, promotor, and titer, it is possible to affect the cell specificity of expression or the expression levels of the protein of interest. Dopamine neurons in the substantia nigra projecting to the striatum, comprising the nigrostriatal pathway, are involved in movement control and degenerate in Parkinson's disease...
February 8, 2017: Genes
https://www.readbyqxmd.com/read/28208679/vanillin-protects-dopaminergic-neurons-against-inflammation-mediated-cell-death-by-inhibiting-erk1-2-p38-and-the-nf-%C3%AE%C2%BAb-signaling-pathway
#19
Xuan Yan, Dian-Feng Liu, Xiang-Yang Zhang, Dong Liu, Shi-Yao Xu, Guang-Xin Chen, Bing-Xu Huang, Wen-Zhi Ren, Wei Wang, Shou-Peng Fu, Ju-Xiong Liu
Neuroinflammation plays a very important role in the pathogenesis of Parkinson's disease (PD). After activation, microglia produce pro-inflammatory mediators that damage surrounding neurons. Consequently, the inhibition of microglial activation might represent a new therapeutic approach of PD. Vanillin has been shown to protect dopaminergic neurons, but the mechanism is still unclear. Herein, we further study the underlying mechanisms in lipopolysaccharide (LPS)-induced PD models. In vivo, we firstly established rat models of PD by unilateral injection of LPS into substantia nigra (SN), and then examined the role of vanillin in motor dysfunction, microglial activation and degeneration of dopaminergic neurons...
February 12, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28208233/neonatal-exposure-to-endocrine-disrupting-chemicals-impair-learning-behaviour-by-disrupting-hippocampal-organization-in-male-swiss-albino-mice
#20
Rakesh Bhaskar, Ashish K Mishra, Banalata Mohanty
Hippocampus is highly susceptible to endocrine disrupting chemicals exposure particularly during the critical phase of brain development. In the present study, mice offspring were exposed to endocrine disruptors mancozeb (MCZ) and imidacloprid (IMI) individually (40 mg MCZ and 0.65 mg IMI/kg/day) as well as to their equimixture (40 mg MCZ + 0.65 mg IMI/kg/day) through the diet of lactating mothers from post-natal day (PND) 1 to PND 28. Half of the randomly selected male offspring were killed at PND 29 and the rest half were left unexposed and killed at PND 63...
February 16, 2017: Basic & Clinical Pharmacology & Toxicology
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