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axon degenerate

Pan Wang, Min Yang, Lu Jiang, Yi-Jun Wu
Organophosphorus compound (OP)-induced delayed neurotoxicity (OPIDN) is characterized by distal axonal degeneration and demyelination of the central and peripheral axons, which leads to progressive muscle weakness, ataxia and paralysis in several days after OP intoxication. This study aimed to investigate the possible use of an imidazole fungicide miconazole as a novel therapy for OPIDN. Adult hens, the most commonly used animal models in OPIDN studies, were orally given tri-o-cresyl phosphate (TOCP). We showed that miconazole, which was administered daily to hens beginning on the 7th day after TOCP exposure, drastically ameliorated the symptoms and histopathological damages in spinal cord and sciatic nerve...
December 13, 2018: Neuropharmacology
Mireia Recasens, Kalpana Shrivastava, Beatriz Almolda, Berta González, Bernardo Castellano
When central nervous system (CNS) homeostasis is altered, microglial cells become rapidly activated, proliferate and release a broad range of molecules. Among the plethora of molecules involved in the regulation of microglial activation, cytokines are considered crucial. Although production of interleukin-10 (IL-10) has been demonstrated after different types of CNS injuries and associated with protective functions, the specific role played by IL-10 modulating microglial cells remains unclear. Hence, the objective of this study was to evaluate the effects of transgenic astrocyte IL-10 production on microglial activation associated with axonal anterograde degeneration...
December 11, 2018: Glia
Yuko Kobayakawa, Katsuhisa Masaki, Ryo Yamasaki, Wataru Shiraishi, Shotaro Hayashida, Shintaro Hayashi, Koichi Okamoto, Takuya Matsushita, Jun-Ichi Kira
Connexin36 (Cx36) forms gap junctions between neurons, which are called electrical synapses, enabling adjacent neurons to communicate directly. The participation of chemical synapses in neurodegeneration in amyotrophic lateral sclerosis (ALS) has long been indicated, but it remains unclear whether electrical synapses are involved in the pathogenesis of ALS. We performed extensive immunopathological analyses using mutant superoxide dismutase 1 (SOD1G93A ) transgenic mice and their littermates to investigate whether Cx36-made electrical synapses are affected in motor neuron diseases...
2018: Frontiers in Neuroscience
Wafaa S Ramadan, Ghada A Abdel-Hamid, Saleh Al-Karim, Noor Ahmed Mubarak Ben Zakar, M-Zaki Elassouli
The outcomes of compressed spinal cord injury (CSCI) necessitate radical treatment. The therapeutic potential of neuroectodermal stem cells (NESCs) in a rat model of CSCI in acute and subacute stages was assessed. White Wistar rat were divided into control, sham-operated, CSCI untreated model, CSCI grafted with NESCs at 1 day after CSCI, and at 7 days after CSCI. Primary NESC cultures were prepared from brains of embryonic day 10 (E10) mice embryos. NESCs were transplanted at the site of injury using a Hamilton syringe...
December 2018: Journal of Biosciences
Deniz Tuna Edizer, Zehra Dönmez, Mehmet Gül, Özgür Yiğit, Birgül Yiğitcan, Turgut Adatepe, Nurten Uzun
OBJECTIVES: To investigate the effects of topical and systemic administrations of melatonin and dexamethasone on facial nerve regeneration. MATERIALS AND METHODS: In total, 50 male albino Wistar rats underwent facial nerve axotomy and neurorrhaphy. The animals were divided into 5 groups: control, topical melatonin, systemic melatonin, topical dexamethasone, and systemic dexamethasone. Nerve conduction studies were performed preoperatively and at 3, 6, 9, and 12 weeks after drug administrations...
December 12, 2018: Journal of International Advanced Otology
Jik Nijssen, Julio Aguila, Rein Hoogstraaten, Nigel Kee, Eva Hedlund
Spinal motor axons traverse large distances to innervate target muscles, thus requiring local control of cellular events for proper functioning. To interrogate axon-specific processes we developed Axon-seq, a refined method incorporating microfluidics, RNA sequencing (RNA-seq), and bioinformatic quality control. We show that the axonal transcriptome is distinct from that of somas and contains fewer genes. We identified 3,500-5,000 transcripts in mouse and human stem cell-derived spinal motor axons, most of which are required for oxidative energy production and ribogenesis...
December 11, 2018: Stem Cell Reports
Nashwa Fathy Gamal El-Tahawy, Sara Mohamed Naguib Abdel Hafez, Maggie M Ramzy, Nagwa M Zenhom, Heba A Abdel-Hamid
Cerebellum seems to be a specific target for both the decrease of estrogen and hypertension in menopause. The aim of this study was to investigate the hypertension and menopause-induced changes in rat's cerebellar cortex and the possible mechanisms of these changes. Rats were divided into four groups: the sham-operated control (SC-group), the ovariectomized (OVX-group), the hypertensive (H-group), and the ovariectomized-hypertensive (OVX-H-group) group. The mean arterial pressure (MAP), serum nitric oxide (NO), lipid peroxides and antioxidant catalase enzyme levels were assayed...
December 7, 2018: Journal of Cellular Physiology
Fatemeh Ghanaatian, Naser-Aldin Lashgari, Amir Hossein Abdolghaffari, Seyed M Rajaee, Yunes Panahi, George E Barreto, Alexandra E Butler, Amirhossein Sahebkar
Multiple sclerosis (MS) is a disease that has shown a considerable increase in prevalence in recent centuries. Current knowledge about its etiology is incomplete, and therefore it cannot be managed optimally utilizing targeted therapeutic regimens at each stage of the disease. MS progresses in different stages, beginning with a cascade of inflammation. The pivotal spark to initiate this cascade seems to be the migration of Th17 into the central nervous system across the blood-brain barrier (BBB) through the disrupted tight junctions...
December 10, 2018: Journal of Cellular Physiology
Shota Yamamoto, Tomohiro Yamashita, Mayu Ito, Jose M M Caaveiro, Nobuaki Egashira, Hidetoshi Tozaki-Saitoh, Makoto Tsuda
Oxaliplatin, which is widely used as chemotherapy for certain solid cancers, frequently causes peripheral neuropathy. Commonly described neuropathic symptoms include aberrant sensations such as mechanical allodynia (hypersensitivity to normally innocuous stimuli). Although oxaliplatin neuropathy is a dose-limiting toxicity, there are no established preventive strategies available at present. By screening several sets of small-molecule chemical libraries (more than 3,000 compounds in total) using a newly established in vitro high-throughput phenotypic assay, we identified fulvestrant, a clinically approved drug for the treatment of breast cancer in postmenopausal women, as having a protective effect on oxaliplatin-induced neuronal damage...
December 4, 2018: International Journal of Cancer. Journal International du Cancer
Deanna L Benson, Bridget A Matikainen-Ankney, Ayan Hussein, George W Huntley
LRRK2 mutation is the most common inherited, autosomal dominant cause of Parkinson's disease (PD) and has also been observed in sporadic cases. Most mutations result in increased LRRK2 kinase activity. LRRK2 is highly expressed in brain regions that receive dense, convergent innervation by dopaminergic and glutamatergic axons, and its levels rise developmentally coincident with glutamatergic synapse formation. The onset and timing of expression suggests strongly that LRRK2 regulates the development, maturation and function of synapses...
December 4, 2018: Biochemical Society Transactions
Felix Fischbach, Julia Nedelcu, Patrizia Leopold, Jiangshan Zhan, Tim Clarner, Lara Nellessen, Christian Beißel, Yasemin van Heuvel, Anand Goswami, Joachim Weis, Bernd Denecke, Christoph Schmitz, Tanja Hochstrasser, Stella Nyamoya, Marion Victor, Cordian Beyer, Markus Kipp
Oligodendrocytes are integral to efficient neuronal signaling. Loss of myelinating oligodendrocytes is a central feature of many neurological diseases, including multiple sclerosis (MS). The results of neuropathological studies suggest that oligodendrocytes react with differing sensitivity to toxic insults, with some cells dying early during lesion development and some cells being resistant for weeks. This proposed graded vulnerability has never been demonstrated but provides an attractive window for therapeutic interventions...
December 3, 2018: Glia
Bob Olsson, Erik Portelius, Nicholas C Cullen, Åsa Sandelius, Henrik Zetterberg, Ulf Andreasson, Kina Höglund, David J Irwin, Murray Grossman, Daniel Weintraub, Alice Chen-Plotkin, David Wolk, Leo McCluskey, Lauren Elman, Leslie M Shaw, Jon B Toledo, Jennifer McBride, Pilar Hernandez-Con, Virginia M-Y Lee, John Q Trojanowski, Kaj Blennow
Importance: Neuronal and axonal destruction are hallmarks of neurodegenerative diseases, but it is difficult to estimate the extent and progress of the damage in the disease process. Objective: To investigate cerebrospinal fluid (CSF) levels of neurofilament light (NFL) protein, a marker of neuroaxonal degeneration, in control participants and patients with dementia, motor neuron disease, and parkinsonian disorders (determined by clinical criteria and autopsy), and determine its association with longitudinal cognitive decline...
December 3, 2018: JAMA Neurology
Won Hwa Kim, Annie M Racine, Nagesh Adluru, Seong Jae Hwang, Kaj Blennow, Henrik Zetterberg, Cynthia M Carlsson, Sanjay Asthana, Rebecca L Koscik, Sterling C Johnson, Barbara B Bendlin, Vikas Singh
In addition to the development of beta amyloid plaques and neurofibrillary tangles, Alzheimer's disease (AD) involves the loss of connecting structures including degeneration of myelinated axons and synaptic connections. However, the extent to which white matter tracts change longitudinally, particularly in the asymptomatic, preclinical stage of AD, remains poorly characterized. In this study we used a novel graph wavelet algorithm to determine the extent to which microstructural brain changes evolve in concert with the development of AD neuropathology as observed using CSF biomarkers...
October 23, 2018: NeuroImage: Clinical
Elliot H Choi, Yadi Xu, Marie Medynets, Maria Chiara G Monaco, Eugene O Major, Avindra Nath, Tongguang Wang
Neuroinflammatory diseases such as multiple sclerosis are characterized by infiltration of lymphocytes into the central nervous system followed by demyelination and axonal degeneration. While evidence suggests that activated T lymphocytes induce neurotoxicity and impair function of neural stem cells, the effect of T cells on oligodendrocyte progenitor cells (OPCs) is still uncertain, partly due to the difficulty in obtaining human OPCs. Here we studied the effect of activated T cells on OPCs using OPCs derived from human hematopoietic stem cells or from human fetal brain...
November 2018: Glia
Xuan Yang, Yuzhang Wu, Bei Zhang, Bing Ni
Multiple sclerosis (MS), a chronic inflammatory demyelinating disease of the central nervous system, is characterized by axonal degeneration and gliosis. Although the causes of MS remain unknown, gene dysregulation in the central nervous system has been associated with the disease pathogenesis. As such, the various regulators of gene expression may be contributing factors. The noncoding (nc) RNAs have piqued the interest of MS researchers due to their known functions in human physiology and various pathological processes, despite being generally characterized as transcripts without apparent protein-coding capacity...
November 29, 2018: Clinical Epigenetics
Ian D Duncan, Abigail B Radcliff, Moones Heidari, Grahame Kidd, Benjamin K August, Lauren A Wierenga
Endogenous remyelination of the CNS can be robust and restore function, yet in multiple sclerosis it becomes less complete with time. Promoting remyelination is a major therapeutic goal, both to restore function and to protect axons from degeneration. Remyelination is thought to depend on oligodendrocyte progenitor cells, giving rise to nascent remyelinating oligodendrocytes. Surviving, mature oligodendrocytes are largely regarded as being uninvolved. We have examined this question using two large animal models...
November 28, 2018: Proceedings of the National Academy of Sciences of the United States of America
Johann Otto Pelz, Elena Belau, Christopher Fricke, Joseph Classen, David Weise
Background: Recent histopathological studies revealed degeneration of the dorsal motor nucleus early in the course of Parkinson's disease (PD). Degeneration of the vagus nerve (VN) axons following neurodegeneration of brainstem vagal nuclei should be detectable by high-resolution ultrasound (HRUS) as a thinning of the VNs. Methods: We measured both VNs cross-sectional area (VN-CSA) of 35 patients with PD and 35 age- and sex-matched healthy controls at the level of the thyroid gland using HRUS. Results: On both sides, the VN-CSA was significantly smaller in PD patients than in controls (right: 2...
2018: Frontiers in Neurology
You Chul Chung, Ji Hee Lim, Hyun Mi Oh, Hyung Wook Kim, Min Young Kim, Eun Nim Kim, Yaeni Kim, Yoon Sik Chang, Hye Won Kim, Cheol Whee Park
Decreased AMPK-eNOS bioavailability mediates the development of diabetic peripheral neuropathy (DPN) through increased apoptosis and decreased autophagy activity in relation to oxidative stress. Schwann cells are responsible for maintaining structural and functional integrity of neurons and for repairing damaged nerves. We evaluated the neuro-protective effect of cinacalcet on DPN by activating the AMPK-eNOS pathway using db/db mice and human Schwann cells (HSCs). Sciatic nerve of db/db mice was characterized by disorganized myelin, axonal shrinkage, and degeneration that were accompanied by marked fibrosis, inflammation, and apoptosis...
November 26, 2018: Cell Death & Disease
S N Illarioshkin, S A Klyushnikov, V A Vigont, Yu A Seliverstov, E V Kaznacheyeva
Huntington's disease (HD) is a severe autosomal dominant neurodegenerative disorder characterized by a combination of motor, cognitive, and psychiatric symptoms, atrophy of the basal ganglia and the cerebral cortex, and inevitably progressive course resulting in death 5-20 years after manifestation of its symptoms. HD is caused by expansion of CAG repeats in the HTT gene, which leads to pathological elongation of the polyglutamine tract within the respective protein - huntingtin. In this review, we present a modern view on molecular biology of HD as a representative of the group of polyglutamine diseases, with an emphasis on conformational changes of mutant huntingtin, disturbances in its cellular processing, and proteolytic stress in degenerating neurons...
September 2018: Biochemistry. Biokhimii︠a︡
Christopher Nishioka, Hsiao-Fang Liang, Barsam Barsamian, Shu-Wei Sun
BACKGROUND: Clinical imaging modalities including optical coherence tomography (OCT) and diffusion tensor imaging (DTI) are vital in Multiple Sclerosis (MS), but their relationships during the different phases of Retinal ganglion cell (RGC) degeneration are not clear. We hypothesize that initial injury in optic nerve causes axonal degeneration leading to RGC loss in retina, which can be characterized by a combination of DTI and OCT. Our objective was to examine the correlation between noninvasive and histological data to chronicle the degeneration profile of RGCs in the retina and optic nerve in a mouse model of MS...
November 13, 2018: Multiple Sclerosis and related Disorders
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