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axon degenerate

Byoung-San Moon, Wange Lu, Hong Ju Park
Hearing loss occurs with the loss of hair cells of the cochlea and subsequent degeneration of spiral ganglion neurons (SGNs). Regeneration of SGNs is a potentially promising therapeutic approach to hearing loss in addition to the use of a cochlear implant (CI), because this device stimulates SGNs directly to restore hearing bypassing the missing hair cells. The presence of SGN-neural stem cells (NSCs) has been reported in adult human and mice. These cells have the potential to become SGNs and thus represent a cellular foundation for regeneration therapies for hearing loss...
August 14, 2018: Biochemical and Biophysical Research Communications
Toshiyuki Araki, Shuji Wakatsuki
ZNRF1 is an E3 ubiquitin ligase constitutively expressed in almost all neurons in the central and peripheral nervous systems during development and in adulthood. From this expression profile, the role of ZNRF1 is assumed to be common to many different types of neurons. We have analyzed the roles of ZNRF1-dependent degradation of target proteins in neurons. In mature neurons, ZNRF1 is activated in response to different types of stress that cause neuronal/axonal degeneration, and degrade AKT to activate GSK3B...
August 14, 2018: Neuroscience Research
Virendra Bhagawan Chine, Ngan Pan Bennett Au, Gajendra Kumar, Chi Him Eddie Ma
Chemotherapy-induced peripheral neuropathy (CIPN) is an irreversible off-target adverse effect of many chemotherapeutic agents such as paclitaxel, yet its mechanism is poorly understood and no preventative measure is available. CIPN is characterized by peripheral nerve damages resulting in permanent sensory function deficits. Our recent unbiased genome-wide analysis revealed that heat shock protein (Hsp) 27 is part of a transcriptional network induced by axonal injury and highly enriched for genes involved in adaptive neuronal responses, particularly axonal regeneration...
August 16, 2018: Molecular Neurobiology
Yuan-Ting Wu, Ashfaq Adnan
As a major cytoskeleton element of the axon, the breaking of microtubules (MTs) has been considered as a major cause of the axon degeneration. High strain rate loading is considered as one of the key factors in microtubule breaking. Due to the small size of microtubule, the real-time behavior of microtubule breaking is hard to capture. This study employs fully-atomistic molecular dynamics (MD) simulation to determine the failure modes of microtubule under different loadings conditions such as, unidirectional stretching, bending and hydrostatic expansion...
August 16, 2018: Scientific Reports
Ione O C Woollacott, Martina Bocchetta, Carole H Sudre, Basil H Ridha, Catherine Strand, Robert Courtney, Sebastien Ourselin, M Jorge Cardoso, Jason D Warren, Martin N Rossor, Tamas Revesz, Nick C Fox, Janice L Holton, Tammaryn Lashley, Jonathan D Rohrer
White matter hyperintensities (WMH) are often seen on MRI brain scans in frontotemporal dementia (FTD) due to progranulin (GRN) mutations, but their pathological correlates are unknown. We examined the histological changes underlying WMH in a patient with GRN mutation associated behavioral variant FTD. In vivo and cadaveric MRI showed progressive, asymmetric frontotemporal and parietal atrophy, and asymmetrical WMH predominantly affecting frontal mid-zones. We first performed segmentation and localization analyses of WMH present on cadaveric MRI FLAIR images, then selected five different brain regions directly matched to differing severities of WMH for histological analysis...
August 16, 2018: Neurocase
Patrizia LoPresti
Oligodendrocytes (OLGs), the myelin-forming cells of the central nervous system (CNS), are lifelong partners of neurons. They adjust to the functional demands of neurons over the course of a lifetime to meet the functional needs of a healthy CNS. When this functional interplay breaks down, CNS degeneration follows. OLG processes are essential features for OLGs being able to connect with the neurons. As many as fifty cellular processes from a single OLG reach and wrap an equal number of axonal segments. The cellular processes extend to meet and wrap axonal segments with myelin...
August 15, 2018: International Journal of Molecular Sciences
Yei Hwan Jung, M Joseph Phillips, Juhwan Lee, Ruosen Xie, Allison L Ludwig, Guojun Chen, Qifeng Zheng, Tong June Kim, Huilong Zhang, Patrick Barney, Jee Min, Katherine Barlow, Shaoqin Gong, David M Gamm, Zhenqiang Ma
Blinding disorders of the outer retina involve dysfunction and degeneration of photoreceptors. One potential approach to treat these forms of blindness is to repopulate the outer retina via a simple bolus injection of donor photoreceptors. However, this may not be ideal due to the highly polarized organization of photoreceptors that include apical light sensing photopigments and basal axon terminals. Furthermore, bolus injections create uncertainty with regard to the area, density, and retention of donor cells...
August 14, 2018: Advanced Materials
P Z Wu, L D Liberman, K Bennett, V de Gruttola, J T O'Malley, M C Liberman
The noise-induced and age-related loss of synaptic connections between auditory-nerve fibers and cochlear hair cells is well-established from histopathology in several mammalian species; however, its prevalence in humans, as inferred from electrophysiological measures, remains controversial. Here we look for cochlear neuropathy in a temporal-bone study of "normal-aging" humans, using autopsy material from 20 subjects aged 0 to 89 yrs, with no history of otologic disease. Cochleas were immunostained to allow accurate quantification of surviving hair cells in the organ Corti and peripheral axons of auditory-nerve fibers...
August 9, 2018: Neuroscience
Krishnadas Madhu, Prakash T
BACKGROUND: During the development of Multiple Sclerosis (MS) there is a marked activation of microglia and astrocyte, leading to progressive inflammation and degeneration of myelin sheath which results in axonal loss and neuron damage. PURPOSE: In this study, we have explored the action of Asiaticoside A against the activated microglia and astrocytes. METHODS: Primary microglia and astrocyte cultures were used for the study and the activity were evaluated using cell proliferation assay, nitrate assay and TNFα estimation using ELISA...
August 8, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Ying Zhu, Anthony C Pappas, Rui Wang, Philip Seifert, Daniel Sun, Tatjana C Jakobs
Purpose: To study age- and intraocular pressure-induced changes in the glial lamina of the murine optic nerve on the ultrastructural level. Methods: Naïve C57bl/6 mice at various ages spanning the time between early adulthood (3 months) and senescence (30 months) were used in this study. In addition, the intraocular pressure (IOP) was increased in a group of young mice by injection of microbeads into the anterior chamber. The unmyelinated segments of the optic nerve containing the glial lamina were prepared for transmission electron microscopy and imaged at high resolution...
August 1, 2018: Investigative Ophthalmology & Visual Science
Carla Roberta Nunes Polachini, Roselia Maria Spanevello, Maria Rosa Chitolina Schetinger, Vera Maria Morsch
Multiple sclerosis (MS) commonly affects young adults and leads to a decreased quality of life due to different signs and symptoms that induce physical, cognitive, social, and psychological challenges. This disease, an autoimmune neurological disorder, is characterized by chronic inflammatory demyelination and axonal degeneration of the central nervous system (CNS). To date, its etiology is unknown. A large number of physiological functions are regulated by the cholinergic system because the acetylcholine (ACh) is released from cholinergic neurons and acts on other neurons, most of them not cholinergic in the brain, as well as in various nonneuronal cells, such as those of the immune system and blood; thus, it is considered an important modulatory pathway of both the central and peripheral nervous systems...
September 15, 2018: Journal of the Neurological Sciences
Mireille Moussaed, Sylvaine Huc-Brandt, Nicolas Cubedo, Michele Silhol, Samy Murat, Marie-Christine Lebart, Gabor Kovacs, Jean-Michel Verdier, Francoise Trousse, Mireille Rossel, Anne Marcilhac
REG-1α, a secreted protein containing a C-type lectin domain, is expressed in various organs and plays different roles in digestive system cells in physiological and pathological conditions. Like other members of the Reg family, REG-1α is expressed also in the brain where it has different functions. For instance, we previously reported that REG-1α regulates neurite outgrowth and is overexpressed during the very early stages of Alzheimer's disease (AD). However, REG-1α function in neural cells during neural degeneration remains unknown...
August 6, 2018: Neurobiology of Disease
H D Rosas, P Wilkens, D H Salat, N D Mercaldo, M Vangel, A Y Yendiki, S M Hersch
Although much prior work has focused on the basal ganglia and cortical pathology that defines Huntington's disease (HD), recent studies have also begun to characterize cerebral white matter damage (Rosas et al., 2006; Dumas et al., 2012; Poudel et al., 2014). In this study, we investigated differences in the large fascicular bundles of the cerebral white matter of gene-positive HD carriers, including pre-manifest individuals and early symptomatic patients, using recently developed diffusion tractography procedures...
2018: NeuroImage: Clinical
Laís Silva Fernandes, Neife Aparecida G Dos Santos, Guilherme Luz Emerick, Antonio Cardozo Dos Santos
Organophosphorus (OPs) compounds have been widely used in agriculture, industry, and household, and the neurotoxicity induced by them is still a cause of concern. The main toxic mechanism of OPs is the inhibition of acetylcholinesterase (AChE); however, the delayed neuropathy induced by OPs (OPIDN) is mediated by other mechanisms such as the irreversible inhibition of 70% of NTE activity (neuropathy target esterase) that leads to axonal degeneration. Liraglutide is a long-lasting GLP-1 analog clinically used as antidiabetic...
August 7, 2018: Neurotoxicity Research
Isidro Ferrer
Oligodendrocytes are in contact with neurons, wrap axons with a myelin sheath that protects their structural integrity, and facilitate nerve conduction. Oligodendrocytes also form a syncytium with astrocytes which interacts with neurons, promoting reciprocal survival mediated by activity and by molecules involved in energy metabolism and trophism. Therefore, oligodendrocytes are key elements in the normal functioning of the central nervous system. Oligodendrocytes are affected following different insults to the central nervous system including ischemia, traumatism, and inflammation...
August 2, 2018: Progress in Neurobiology
Ximeng Yang, Chihiro Tohda
We previously found diosgenin, an herbal drug-derived steroid sapogenin, to be remarkably effective at restoring Aβ-induced axonal degeneration and improving memory function in model of Alzheimer's disease (AD), 5XFAD mouse. In this study, we investigated the downstream signaling of diosgenin and explored new therapeutic targets in AD. We showed that the expression of heat shock cognate (HSC) 70 was increased in Aβ-treated neurons and in 5XFAD mice but was decreased by diosgenin treatment. In addition, knockdown of HSC70 significantly promoted axonal growth in neurons...
August 3, 2018: Scientific Reports
Christina Mayer, Claus Bruehl, Emma L Salt, Ricarda Diem, Andreas Draguhn, Richard Fairless
Retinal ganglion cells (RGCs), a diverse body of neurons which relay visual signals from the retina to the higher processing regions of the brain, are susceptible to neurodegenerative processes in several diseases affecting the retina. Previous evidence shows that RGCs are damaged at early stages of autoimmune optic neuritis, prior to subsequent degeneration of the optic nerve. In order to study cell type-specific vulnerability of RGCs we performed immunohistochemical and patch clamp electrophysiological analyses of RGCs following induction of autoimmune optic neuritis using the experimental autoimmune encephalomyelitis model in Brown Norway rats...
July 31, 2018: Neuroscience
Carla A Wicki, James V M Hanson, Sven Schippling
PURPOSE OF REVIEW: Optical coherence tomography (OCT) is a noninvasive in-vivo imaging tool that enables the quantification of the various retinal layer thicknesses. Given the frequent involvement of the visual pathway in multiple sclerosis, OCT has become an important tool in clinical practice, research and clinical trials. In this review, the role of OCT as a means to investigate visual pathway damage in multiple sclerosis is discussed. RECENT FINDINGS: Evidence from recent OCT studies suggests that the peripapillary retinal nerve fibre layer (pRNFL) appears to be an ideal marker of axonal integrity, whereas the macular ganglion cell and inner plexiform layer (GCIP) thickness enables early detection of neuronal degeneration in multiple sclerosis...
July 31, 2018: Current Opinion in Neurology
Juliette Hordeaux, Christian Hinderer, Tamara Goode, Nathan Katz, Elizabeth L Buza, Peter Bell, Roberto Calcedo, Laura K Richman, James M Wilson
Mucopolysaccharidosis type I is a recessive genetic disease caused by deficiency of the lysosomal enzyme α-L-iduronidase, which leads to a neurodegenerative and systemic disease called Hurler syndrome in its most severe form. Several clinical trials are evaluating adeno-associated virus serotype 9 (AAV9) for the treatment of neurodegenerative diseases. Although these trials focus on systemic or lumbar administration, intrathecal administration via suboccipital puncture into the cisterna magna has demonstrated remarkable efficacy in large animals...
September 21, 2018: Molecular Therapy. Methods & Clinical Development
Bérangère Deleglise, Benjamin Lassus, Vanessa Soubeyre, Mohamed Doulazmi, Bernard Brugg, Peter Vanhoutte, Jean-Michel Peyrin
Increasing evidence suggests that pathological hallmarks of chronic degenerative syndromes progressively spread among interconnected brain areas in a disease-specific stereotyped pattern. Functional brain imaging from patients affected by various neurological syndromes such as traumatic brain injury and stroke indicates that the progression of such diseases follows functional connections, rather than simply spreading to structurally adjacent areas. Indeed, initial damage to a given brain area was shown to disrupt the communication in related brain networks...
August 2, 2018: Scientific Reports
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