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amyloid precursor protein spinal cord

Qiuju Yuan, Jian Yang, Wutian Wu, Zhi-Xiu Lin
There have been an increasing number of reports of non-cognitive symptoms in Alzheimer's disease (AD). Some symptoms are associated with the loss of motor functions, e.g. gait disturbances, disturbed activity level and balance. Consistent with clinical findings, several AD mouse models harboring amyloid pathology develop motor impairment. Although the factors that contribute to the motor deficits have not yet been determined, it has been suggested that axonopathy is one of the key factors that may contribute to this particular feature of the disease...
June 9, 2017: Oncotarget
Malgorzata Ciurkiewicz, Vanessa Herder, Muhammad Akram Khan, Ann-Kathrin Uhde, René Teich, Stephan Floess, Wolfgang Baumgärtner, Jochen Huehn, Andreas Beineke
Theiler's murine encephalomyelitis (TME) of susceptible mouse strains is a commonly used infectious animal model for multiple sclerosis. The study aim was to test the hypothesis whether cytotoxic T cell responses account for the limited impact of regulatory T cells on antiviral immunity in TME virus-induced demyelinating disease (TMEV-IDD) resistant C57BL/6 mice. TME virus-infected C57BL/6 mice were treated with (i) interleukin-2/-anti-interleukin-2-antibody-complexes to expand regulatory T cells ('Treg-expansion'), (ii) anti-CD8-antibodies to deplete cytotoxic T cells ('CD8-depletion') or (iii) with a combination of Treg-expansion and CD8-depletion ('combined treatment') prior to infection...
April 27, 2017: Brain Pathology
Shao Li, Xi Wang, Quan-Hong Ma, Wu-Lin Yang, Xiao-Gang Zhang, Gavin S Dawe, Zhi-Cheng Xiao
Amyloid precursor protein (APP), commonly associated with Alzheimer's disease, also marks axonal degeneration. In the recent studies, we demonstrated that APP aggregated at nodes of Ranvier (NORs) in myelinated central nervous system (CNS) axons and interacted with Nav1.6. However, the physiological function of APP remains unknown. In this study, we described reduced sodium current densities in APP knockout hippocampal neurons. Coexpression of APP or its intracellular domains containing a VTPEER motif with Nav1...
December 23, 2016: Scientific Reports
Jing Xu, Jian He, Huang He, Renjun Peng, Jian Xi
This study was intended to compare the therapeutic efficacies of NEP1-40 and SiNgR199 on treating spinal cord injury (SCI). Nogo-A, growth associated protein 43 (GAP-43), microtubule associated protein 2 (MAP-2), and amyloid βA4 precursor protein (APP) expressions were determined using western blot and quantitative PCR. Neurite outgrowth detected the growth of neurites, and BDA anterograde tracing was used to label the regenerated axonal. Rats' behavior was assessed with Basso, Beattie, and Bresnahan locomotor rating scale (BBB)...
December 5, 2016: Molecular Neurobiology
Katharina Marie Höflich, Cordian Beyer, Tim Clarner, Christoph Schmitz, Stella Nyamoya, Markus Kipp, Tanja Hochstrasser
Axonal damage has been identified as a significant contributor to permanent clinical disability in multiple sclerosis. In the context of demyelinating disorders, this destructive event can be the result of inflammation, demyelination and/or the activation of innate defense cells such as microglia or monocytes. The relative contribution of each of these variables to acute axonal injury is, however, unknown. In the present study, we compared the extent of acute axonal damage in three different murine demyelination models using anti-amyloid precursor protein (APP) immunohistochemistry...
November 1, 2016: Brain Research
Frauke Seehusen, Kirsten Kiel, Stefano Jottini, Peter Wohlsein, Andre Habierski, Katharina Seibel, Tanja Vogel, Henning Urlaub, Martin Kollmar, Wolfgang Baumgärtner, Ulrike Teichmann
Dystonia musculorum is a neurodegenerative disorder caused by a mutation in the dystonin gene. It has been described in mice and humans where it is called hereditary sensory autonomic neuropathy. Mutated mice show severe movement disorders and die at the age of 3-4 weeks. This study describes the discovery and molecular, clinical, as well as pathological characterization of a new spontaneously occurring mutation in the dystonin gene in C57BL/6N mice. The mutation represents a 40-kb intragenic deletion allele of the dystonin gene on chromosome 1 with exactly defined deletion borders...
September 2016: Genetics
Yanjun Guo, Luning Wang, Mingwei Zhu, Honghong Zhang, Yazhuo Hu, Zhitao Han, Jia Liu, Weiqin Zhao, Dexin Wang
The aim of this study was to investigate the neuropathological features of the spinal cord in patients suffering with Alzheimer's disease (AD). Spinal cord tissue collected from three AD patients and eight controls was selected for the study. Data were collected at T2, T8, T10, L4, and S2 spinal levels. The sections were subjected to hematoxylin and eosin and Gallyas-Braak staining methods and then were immunostained with antibodies such as phosphorylated tau protein (AT8), α-synuclein, Aβ, amyloid precursor protein, ubiquitin, and TDP-43...
2016: Neuropsychiatric Disease and Treatment
Srinivasu Kallakuri, Heena S Purkait, Satya Dalavayi, Pamela VandeVord, John M Cavanaugh
INTRODUCTION: Blast induced neurotrauma has been the signature wound in returning soldiers from the ongoing wars in Iraq and Afghanistan. Of importance is understanding the pathomechansim(s) of blast overpressure (OP) induced axonal injury. Although several recent animal models of blast injury indicate the neuronal and axonal injury in various brain regions, animal studies related to axonal injury in the white matter (WM) tracts of cervical spinal cord are limited. OBJECTIVE: The purpose of this study was to assess the extent of axonal injury in WM tracts of cervical spinal cord in male Sprague Dawley rats subjected to a single insult of blast OP...
October 2015: Journal of Neurosciences in Rural Practice
D M Hanshaw, J W Finnie, J Manavis, A E Kessell
CASE REPORT: An 18-month-old Angus cow presented with rapidly developing ataxia and subsequently died. The finding of large numbers of axonal spheroids in brainstem nuclei and spinal cord grey matter, bilaterally symmetrical in distribution, was consistent with a histopathological diagnosis of neuroaxonal dystrophy (NAD). Most of the axonal swellings were immunopositive to amyloid precursor protein, suggesting that interruption to axonal flow was important in their genesis. CONCLUSIONS: The topographical distribution of axonal spheroids in the brain and spinal cord in this bovine case closely resembled that found in the ovine neurodegenerative disorder termed NAD, in which axonal swellings are the major pathological feature...
August 2015: Australian Veterinary Journal
Alexander E Ropper, Xiang Zeng, Jamie E Anderson, Dou Yu, InBo Han, Hariprakash Haragopal, Yang D Teng
We report an efficient and effective device to reproducibly model clinically relevant spinal cord injury (SCI) via controlled mechanical compression. In the present study, following skin incision, dorsal laminectomy was performed to expose T10 spinal cord of adult female Sprague-Dawley rats (230-250 g). The vertebral column was suspended and stabilized by Allis clamps at T8 and 12 spinous processes. A metal impounder was then gently loaded onto T10 dura (20, 35 or 50 g × 5 min; n=7/group), resulting in acute mild, moderate, or severe standing weight compression, respectively...
September 2015: Experimental Neurology
Yasuyuki Honjo, Takashi Ayaki, Takami Tomiyama, Tomohisa Horibe, Hidefumi Ito, Hiroshi Mori, Ryosuke Takahashi, Koji Kawakami
Alzheimer's disease (AD) is characterized by the accumulation of amyloid-β (Aβ) and abnormally phosphorylated tau which contribute to endoplasmic reticulum (ER) stress. Previous studies demonstrated that Aβ and a truncated fragment of Aβ induced death of oligodendrocytes in vitro. In addition, a triple-transgenic AD mouse model exhibits significant region-specific alterations in myelination patterns at time points preceding the appearance of Aβ accumulation. The growth arrest and DNA damage protein (GADD) 34 is up-regulated in response to ER stress and regulates subunit of protein phosphatase 1 (PP1) complex that dephosphorylates eukaryotic translation initiator factor 2α (elF2α)...
August 18, 2015: Neuroscience Letters
M C Gonzalez Deniselle, L Garay, M Meyer, G Gargiulo-Monachelli, F Labombarda, S Gonzalez, R Guennoun, M Schumacher, Alejandro F De Nicola
Far beyond its role in reproduction, progesterone exerts neuro-protective, promyelinating, and anti-inflammatory effects in the nervous system. These effects are amplified under pathological conditions, implying that changes of the local environment sensitize nervous tissues to steroid therapy. The present survey covers our results of progesterone neuroprotection in a motoneuron neurodegeneration model and a neuroinflammation model. In the degenerating spinal cord of the Wobbler mouse, progesterone reverses the impaired expression of neurotrophins, increases enzymes of neurotransmission and metabolism, prevents oxidative damage of motoneurons and their vacuolar degeneration (paraptosis), and attenuates the development of mitochondrial abnormalities...
October 1, 2011: Hormone Molecular Biology and Clinical Investigation
Yanan Chu, Xuehua Peng, Zhiming Long, Kejian Wang, Shifang Luo, Akhilesh Sharma, Guiqiong He
The γ-secretase complex catalyzes the final cleavage step of amyloid β-protein precursor (APP) to generate amyloid β (Aβ) peptide, a pathogenic component of senile plaques in the brain of Alzheimer's disease (AD) patients. Recent studies have shown that presenilin enhancer-2 (Pen-2), presenilin (PS, including PS1 and PS2), nicastrin, and anterior pharynx-defective 1 are essential components of the γ-secretase. The structure and function of Pen-2 in vitro have been well defined. However, little is known about the neuroanatomical distribution and expression of Pen-2 in the central nervous system (CNS) of AD model mice...
April 2015: Acta Biochimica et Biophysica Sinica
De-En Xu, Wen-Min Zhang, Zara Zhuyun Yang, Hong-Mei Zhu, Ke Yan, Shao Li, Dominique Bagnard, Gavin S Dawe, Quan-Hong Ma, Zhi-Cheng Xiao
Amyloid precursor protein (APP), commonly associated with Alzheimer disease, is upregulated and distributes evenly along the injured axons, and therefore, also known as a marker of demyelinating axonal injury and axonal degeneration. However, the physiological distribution and function of APP along myelinated axons was unknown. We report that APP aggregates at nodes of Ranvier (NOR) in the myelinated central nervous system (CNS) axons but not in the peripheral nervous system (PNS). At CNS NORs, APP expression co-localizes with tenascin-R and is flanked by juxtaparanodal potassium channel expression demonstrating that APP localized to NOR...
2014: Cell Adhesion & Migration
Maja Klevanski, Martina Saar, Frederik Baumkötter, Sascha W Weyer, Stefan Kins, Ulrike C Müller
The analysis of mouse models indicated that APP and the related APLPs are important for synapse formation and function. The synaptic role of APP is, however, complex due to partially overlapping functions within the gene family. APP/APLPs are proteolytically cleaved and have both adhesive and signaling properties. Mice lacking individual APP family members are viable, whereas APP/APLP2 and APLP1/APLP2 double knockout (DKO) mice die shortly after birth. Here, we analyzed the morphology of the neuromuscular junction (NMJ) of lethal APLP1/APLP2-DKO mice in comparison to lethal APP/APLP2-DKO mutants and viable single KO mice...
July 2014: Molecular and Cellular Neurosciences
Spencer Moore, Anna J Khalaj, Rhusheet Patel, JaeHee Yoon, Daniel Ichwan, Liat Hayardeny, Seema K Tiwari-Woodruff
Glatiramer acetate (GA; Copaxone) is an approved drug for the treatment of multiple sclerosis (MS). The underlying multifactorial anti-inflammatory, neuroprotective effect of GA is in the induction of reactive T cells that release immunomodulatory cytokines and neurotrophic factors at the injury site. These GA-induced cytokines and growth factors may have a direct effect on axon function. Building on previous findings that suggest a neuroprotective effect of GA, we assessed the therapeutic effects of GA on brain and spinal cord pathology and functional correlates using the chronic experimental autoimmune encephalomyelitis (EAE) mouse model of MS...
December 2014: Journal of Neuroscience Research
Feng Tan, Jie Chen, Yangui Liang, Minhua Gu, Yanping Li, Xuewen Wang, DI Meng
Cerebral ischemia induces injury, not only in the ischemic core and surrounding penumbra tissues, but also in remote areas such as the cervical spinal cord. The aim of the present study was to determine the effects of electroacupuncture (EA) on cervical spinal cord injury following cerebral ischemia/reperfusion in stroke-prone renovascular hypertensive (RHRSP) rats. The results demonstrated that neuronal loss, which was assayed by Nissl staining in the cervical spinal cords of RHRSP rats subjected to transient middle cerebral artery occlusion (MCAO), was markedly decreased by EA stimulation at the GV20 (Baihui) and GV14 (Dazhui) acupoints compared with that in rats undergoing sham stimulation...
June 2014: Experimental and Therapeutic Medicine
De-En Xu, Wen-Min Zhang, Zara Zhuyun Yang, Hong-Mei Zhu, Ke Yan, Shao Li, Dominique Bagnard, Gavin S Dawe, Quan-Hong Ma, Zhi-Cheng Xiao
Amyloid precursor protein (APP), commonly associated with Alzheimer disease, is upregulated and distributes evenly along the injured axons, and therefore, also known as a marker of demyelinating axonal injury and axonal degeneration. However, the physiological distribution and function of APP along myelinated axons was unknown. We report that APP aggregates at nodes of Ranvier (NOR) in the myelinated central nervous system (CNS) axons but not in the peripheral nervous system (PNS). At CNS NORs, APP expression co-localizes with tenascin-R and is flanked by juxtaparanodal potassium channel expression demonstrating that APP localized to NOR...
April 11, 2014: Cell Adhesion & Migration
Shawn Albers, Fatima Inthathirath, Sandeep K Gill, Warren Winick-Ng, Ewa Jaworski, Daisy Y L Wong, Robert Gros, R Jane Rylett
Alzheimer disease (AD) is associated with increased amyloidogenic processing of amyloid precursor protein (APP) to β-amyloid peptides (Aβ), cholinergic neuron loss with decreased choline acetyltransferase (ChAT) activity, and cognitive dysfunction. Both 69-kDa ChAT and 82-kDa ChAT are expressed in cholinergic neurons in human brain and spinal cord with 82-kDa ChAT localized predominantly to neuronal nuclei, suggesting potential alternative functional roles for the enzyme. By gene microarray analysis, we found that 82-kDa ChAT-expressing IMR32 neural cells have altered expression of genes involved in diverse cellular functions...
September 2014: Neurobiology of Disease
Davide Chiasserini, Jan R T van Weering, Sander R Piersma, Thang V Pham, Arjan Malekzadeh, Charlotte E Teunissen, Heidi de Wit, Connie R Jiménez
Extracellular vesicles (EVs) are present in human cerebrospinal fluid (CSF), yet little is known about their protein composition. The aim of this study is to provide a comprehensive analysis of the proteome of CSF EVs by electron microscopy and high resolution tandem mass spectrometry (MS/MS) in conjunction with bioinformatics. We report an extensive catalog of 1315 proteins identified in EVs isolated from two different CSF pools by ultracentrifugation, including 230 novel EV proteins. Out of 1315 proteins, 760 were identified in both CSF pools and about 30% of those were also quantitatively enriched in the EV fraction versus the soluble CSF fraction...
June 25, 2014: Journal of Proteomics
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