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https://www.readbyqxmd.com/read/27933416/positron-emission-tomography-in-amyotrophic-lateral-sclerosis-towards-targeting-of-molecular-pathological-hallmarks
#1
Stefanie M A Willekens, Donatienne Van Weehaeghe, Philip Van Damme, Koen Van Laere
During the past decades, extensive efforts have been made to expand the knowledge of amyotrophic lateral sclerosis (ALS). However, clinical translation of this research, in terms of earlier diagnosis and improved therapy, remains challenging. Since more than 30% of motor neurons are lost when symptoms become clinically apparent, techniques allowing non-invasive, in vivo detection of motor neuron degeneration are needed in the early, pre-symptomatic disease stage. Furthermore, it has become apparent that non-motor signs play an important role in the disease and there is an overlap with cognitive disorders, such as frontotemporal dementia (FTD)...
December 8, 2016: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/27932977/human-neural-stem-cell-transplantation-rescues-cognitive-defects-in-app-ps1-model-of-alzheimer-s-disease-by-enhancing-neuronal-connectivity-and-metabolic-activity
#2
Xueyuan Li, Hua Zhu, Xicai Sun, Fuxing Zuo, Jianfeng Lei, Zhanjing Wang, Xinjie Bao, Renzhi Wang
Alzheimer's disease (AD), the most frequent type of dementia, is featured by Aβ pathology, neural degeneration and cognitive decline. To date, there is no cure for this disease. Neural stem cell (NSC) transplantation provides new promise for treating AD. Many studies report that intra-hippocampal transplantation of murine NSCs improved cognition in rodents with AD by alleviating neurodegeneration via neuronal complement or replacement. However, few reports examined the potential of human NSC transplantation for AD...
2016: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/27932942/loss-of-fractalkine-signaling-exacerbates-axon-transport-dysfunction-in-a-chronic-model-of-glaucoma
#3
Kevin T Breen, Sarah R Anderson, Michael R Steele, David J Calkins, Alejandra Bosco, Monica L Vetter
Neurodegeneration in glaucoma results in decline and loss of retinal ganglion cells (RGCs), and is associated with activation of myeloid cells such as microglia and macrophages. The chemokine fractalkine (FKN or Cx3cl1) mediates communication from neurons to myeloid cells. Signaling through its receptor Cx3cr1 has been implicated in multiple neurodegenerative diseases, but the effects on neuronal pathology are variable. Since it is unknown how FKN-mediated crosstalk influences RGC degeneration in glaucoma, we assessed this in a chronic mouse model, DBA/2J...
2016: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/27931265/increased-caspase-6-activity-in-the-human-anterior-olfactory-nuclei-of-the-olfactory-bulb-is-associated-with-cognitive-impairment
#4
Benedicte Foveau, Steffen Albrecht, David A Bennett, José A Correa, Andrea C LeBlanc
Abnormally elevated hippocampal Caspase-6 (Casp6) activity is intimately associated with age-related cognitive impairment in humans and in mice. In humans, these high levels of Casp6 activity are initially localized in the entorhinal cortex, the area of the brain first affected by the formation of neurofibrillary tangles, according to Braak staging. The reason for the high vulnerability of entorhinal cortex neurons to neurofibrillary tangle pathology and Casp6 activity is unknown. Casp6 activity is involved in axonal degeneration, therefore, one possibility to explain increased vulnerability of the entorhinal cortex neurons would be that the afferent neurons of the olfactory bulb, some of which project their axons to the entorhinal cortex, are equally degenerating...
December 8, 2016: Acta Neuropathologica Communications
https://www.readbyqxmd.com/read/27930290/gamma-motor-neurons-survive-and-exacerbate-alpha-motor-neuron-degeneration-in-als
#5
Melanie Lalancette-Hebert, Aarti Sharma, Alexander K Lyashchenko, Neil A Shneider
The molecular and cellular basis of selective motor neuron (MN) vulnerability in amyotrophic lateral sclerosis (ALS) is not known. In genetically distinct mouse models of familial ALS expressing mutant superoxide dismutase-1 (SOD1), TAR DNA-binding protein 43 (TDP-43), and fused in sarcoma (FUS), we demonstrate selective degeneration of alpha MNs (α-MNs) and complete sparing of gamma MNs (γ-MNs), which selectively innervate muscle spindles. Resistant γ-MNs are distinct from vulnerable α-MNs in that they lack synaptic contacts from primary afferent (IA) fibers...
December 7, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27929803/an-autopsy-verified-case-of-ftld-tdp-type-a-with-upper-motor-neuron-predominant-motor-neuron-disease-mimicking-mm2-thalamic-type-sporadic-creutzfeldt-jakob-disease
#6
Yuichi Hayashi, Yasushi Iwasaki, Akira Takekoshi, Nobuaki Yoshikura, Takahiko Asano, Maya Mimuro, Akio Kimura, Katsuya Satoh, Tetsuyuki Kitamoto, Mari Yoshida, Takashi Inuzuka
Here we report an autopsy-verified case of frontotemporal lobar degeneration (FTLD)-transactivation responsive region (TAR) DNA binding protein (TDP) type A with upper motor neuron-predominant motor neuron disease mimicking MM2-thalamic-type sporadic Creutzfeldt-Jakob disease (sCJD). A 69-year-old woman presented with an 11-month history of progressive dementia, irritability, insomnia, and gait disturbance without a family history of dementia or prion disease. Neurological examination revealed severe dementia, frontal signs, and exaggerated bilateral tendon reflexes...
November 2016: Prion
https://www.readbyqxmd.com/read/27929040/involvement-of-p2x7-receptor-in-neuronal-degeneration-triggered-by-traumatic-injury
#7
Francisco M Nadal-Nicolás, Caridad Galindo-Romero, Francisco J Valiente-Soriano, María Barberà-Cremades, Carlos deTorre-Minguela, Manuel Salinas-Navarro, Pablo Pelegrín, Marta Agudo-Barriuso
Axonal injury is a common feature of central nervous system insults that culminates with the death of the affected neurons, and an irreversible loss of function. Inflammation is an important component of the neurodegenerative process, where the microglia plays an important role by releasing proinflammatory factors as well as clearing the death neurons by phagocytosis. Here we have identified the purinergic signaling through the P2X7 receptor as an important component for the neuronal death in a model of optic nerve axotomy...
December 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27928708/withania-somnifera-reverses-transactive-response-dna-binding-protein-43-proteinopathy-in-a-mouse-model-of-amyotrophic-lateral-sclerosis-frontotemporal-lobar-degeneration
#8
Kallol Dutta, Priyanka Patel, Reza Rahimian, Daniel Phaneuf, Jean-Pierre Julien
Abnormal cytoplasmic mislocalization of transactive response DNA binding protein 43 (TARDBP or TDP-43) in degenerating neurons is a hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U). Our previous work suggested that nuclear factor kappa B (NF-κB) may constitute a therapeutic target for TDP-43-mediated disease. Here, we investigated the effects of root extract of Withania somnifera (Ashwagandha), an herbal medicine with anti-inflammatory properties, in transgenic mice expressing a genomic fragment encoding human TDP-43(A315T) mutant...
December 7, 2016: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/27923201/synthesis-and-biological-evaluation-of-a-new-class-of-benzothiazines-as-neuroprotective-agents
#9
Alessandra Mancini, Alessia Chelini, Angela Di Capua, Loretta Castelli, Simone Brogi, Marco Paolino, Germano Giuliani, Andrea Cappelli, Maria Frosini, Lorenzo Ricci, Erminia Leonelli, Gianluca Giorgi, Antonio Giordani, Jacopo Magistretti, Maurizio Anzini
Neurodegenerative diseases are disorders related to the degeneration of central neurons that gradually lead to various, severe alterations of cognitive and/or motor functions. Currently, for no such diseases does any pharmacological treatment exist able to arrest its progression. Riluzole (1) is a small molecule able to interfere with multiple cellular and molecular mechanisms of neurodegeneration, and is the only approved treatment of amyotrophic lateral sclerosis (ALS), the progression of which proved to significantly slow, thus increasing somewhat average survival...
November 27, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27923065/mutations-in-the-heme-exporter-flvcr1-cause-sensory-neurodegeneration-with-loss-of-pain-perception
#10
Deborah Chiabrando, Marco Castori, Maja di Rocco, Martin Ungelenk, Sebastian Gießelmann, Matteo Di Capua, Annalisa Madeo, Paola Grammatico, Sophie Bartsch, Christian A Hübner, Fiorella Altruda, Lorenzo Silengo, Emanuela Tolosano, Ingo Kurth
Pain is necessary to alert us to actual or potential tissue damage. Specialized nerve cells in the body periphery, so called nociceptors, are fundamental to mediate pain perception and humans without pain perception are at permanent risk for injuries, burns and mutilations. Pain insensitivity can be caused by sensory neurodegeneration which is a hallmark of hereditary sensory and autonomic neuropathies (HSANs). Although mutations in several genes were previously associated with sensory neurodegeneration, the etiology of many cases remains unknown...
December 2016: PLoS Genetics
https://www.readbyqxmd.com/read/27921254/the-impact-of-vitamin-d-supplementation-on-neurodegeneration-tnf-%C3%AE-concentration-in-hypothalamus-and-csf-to-plasma-ratio-of-insulin-in-high-fat-diet-induced-obese-rats
#11
Ghazaleh Nameni, Ghazaleh Hajiluian, Parviz Shahabi, Mahdieh Abbasalizad Farhangi, Mehran Mesgari-Abbasi, Mohammad-Reza Hemmati, Seyed Mahdi Vatandoust
There is growing evidence that obesity can lead to neurodegeneration induced by pro-inflammatory cytokines such as tumor necrosis factor (TNF-α). Moreover, obesity is associated with reduced transport of insulin through the blood-brain barrier (BBB). Insulin deficiency in the brain especially in the hypothalamus region has neurodegenerative and obesity-promoting effects. Because of the anti-inflammatory and neuroprotective effects of vitamin D, in the current experimental study, we aimed to investigate the effects of vitamin D supplementation on neurodegeneration, TNF-α concentration in the hypothalamus, and cerebrospinal fluid (CSF) to serum ratio of insulin in high-fat-diet-induced obese rats...
December 6, 2016: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/27920424/ultrastructural-characterization-of-the-lower-motor-system-in-a-mouse-model-of-krabbe-disease
#12
Valentina Cappello, Laura Marchetti, Paola Parlanti, Silvia Landi, Ilaria Tonazzini, Marco Cecchini, Vincenzo Piazza, Mauro Gemmi
Krabbe disease (KD) is a neurodegenerative disorder caused by the lack of β- galactosylceramidase enzymatic activity and by widespread accumulation of the cytotoxic galactosyl-sphingosine in neuronal, myelinating and endothelial cells. Despite the wide use of Twitcher mice as experimental model for KD, the ultrastructure of this model is partial and mainly addressing peripheral nerves. More details are requested to elucidate the basis of the motor defects, which are the first to appear during KD onset. Here we use transmission electron microscopy (TEM) to focus on the alterations produced by KD in the lower motor system at postnatal day 15 (P15), a nearly asymptomatic stage, and in the juvenile P30 mouse...
December 2016: Scientific Reports
https://www.readbyqxmd.com/read/27919728/voluntary-running-improves-depressive-behaviours-and-the-structure-of-the-hippocampus-in-rats-a-possible-impact-of-myokines
#13
Magda A Eldomiaty, Shaima M Almasry, Maha K Desouky, Sami A Algaidi
This study investigated the impact of voluntary exercise on depressive behaviours, serum and hippocampal levels of myokines, and histopathological features of hippocampal formation in rats. Depressed rats were allowed to voluntarily run on a wheel for 3 weeks. Locomotor activity was assessed by a forced swimming test and the myokine levels in sera and hippocampal homogenates were measured using Enzyme-linked Immunosorbent Assay. Brain sections were analysed for hippocampal structure and neuronal counts. Voluntary running produced significant increase in the distance moved by rats and significant decrease in immobility duration...
December 2, 2016: Brain Research
https://www.readbyqxmd.com/read/27918332/isoflurane-impairs-motor-function-recovery-by-increasing-neuroapoptosis-and-degeneration-during-spinal-ischemia-reperfusion-injury-in-rats
#14
Shih-Yuan Fang, Jung-Shun Lee, Jun-Neng Roan, Yu-Chuan Tsai, Chen-Fuh Lam
BACKGROUND: Spinal cord ischemia (SCI) leads to variable degrees of neurologic deficit in patients undergoing major cardiovascular surgery. The effect of intraoperative neuroprotection against SCI and the subsequent ischemia-reperfusion injury is still limited. Because isoflurane is a commonly used anesthetic agent during major operation, and its neuroprotective and neurotoxicity effects have both been discussed, this study aimed to investigate the effect of isoflurane on the spinal cord's functional recovery in a rat model of cord ischemia...
December 1, 2016: Anesthesia and Analgesia
https://www.readbyqxmd.com/read/27916963/neuron-stimulation-device-integrated-with-silicon-nanowire-based-photodetection-circuit-on-a-flexible-substrate
#15
Suk Won Jung, Jong Yoon Shin, Kilwha Pi, Yong Sook Goo, Dong-Il Dan Cho
This paper proposes a neural stimulation device integrated with a silicon nanowire (SiNW)-based photodetection circuit for the activation of neurons with light. The proposed device is comprised of a voltage divider and a current driver in which SiNWs are used as photodetector and field-effect transistors; it has the functions of detecting light, generating a stimulation signal in proportion to the light intensity, and transmitting the signal to a micro electrode. To show the applicability of the proposed neural stimulation device as a high-resolution retinal prosthesis system, a high-density neural stimulation device with a unit cell size of 110 × 110 μ m and a resolution of 32 × 32 was fabricated on a flexible film with a thickness of approximately 50 μm...
December 1, 2016: Sensors
https://www.readbyqxmd.com/read/27915581/ftld-tdp-and-progressive-supranuclear-palsy-in-comorbidity-a-report-of-two-cases-with-different-clinical-presentations
#16
Kateřina Storey, Silvie Johanidesová, Radoslav Matěj, Jiří Keller, Zdeněk Rohan, Robert Rusina
Frontotemporal lobar degeneration with transactive response DNA-binding protein 43 (FTLD-TDP) and progressive supranuclear palsy (PSP) are distinct neurodegenerations with different clinical presentations. We report two cases with FTLD-TDP and PSP in comorbidity: a patient with amnestic dementia developing frontal lobe dementia, Parkinsonism and supranuclear gaze palsy and a patient with cerebellar ataxia and nystagmus developing akinesia, rigidity, and subcortical dementia. Neuropathological examination revealed neuronal and glial tau pathology together with ubiquitin, and phospho-TDP-43-immunoreactivities in the hippocampus, striatum, mesencephalon, and frontal and temporal cortices...
December 3, 2016: Neurocase
https://www.readbyqxmd.com/read/27915043/involvement-of-bdnf-trkb-signaling-in-the-effect-of-diphenyl-diselenide-on-motor-function-in-a-parkinson-s-disease-rat-model
#17
Tuane Bazanella Sampaio, Simone Pinton, Juliana Trevisan da Rocha, Bibiana Mozzaquatro Gai, Cristina Wayne Nogueira
Parkinson's disease is a progressive neurodegenerative disorder characterized by degeneration of nigrostriatal dopaminergic neurons. Diphenyl diselenide [(PhSe)2] is a compound with pharmacological proprieties, such as antidepressant and neuroprotective. Therefore, this study investigated whether (PhSe)2 reverses motor impairment and neurochemical alterations in a model of Parkinson's disease induced by 6-hydroxydopamine (6-OHDA) in rats. For this, male Wistar rats received 20μg/3μl of 6-OHDA or vehicle into the right striatum...
November 30, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27913184/tolerance-of-hyperammonemia-in-brain-of-heteropneustes-fossilis-is-supported-by-glutamate-glutamine-cycle
#18
Suman Mishra, Rajnikant Mishra
This report presents analysis of molecular switches associated with tolerance to hyperammonemia in Heteropneustes fossilis because it tolerates about 100-fold more ammonia than mammals. Brains of Heteropneustes fossilis exposed to 100mM ammonium chloride were dissected after Zero hour as control, 16hrs and 20hrs exposure. The status of neuron and glia were analysed by Golgi staining, Luxol Fast Blue, and Nissl's staining. The expression patterns of genes associated to homeostasis of neuron and glia, management of oxidative stress and inflammation, ammonia metabolism and brain derived neurotrophic factor were analysed through reverse-transcriptase-polymerase chain reaction...
November 29, 2016: Journal of Chemical Neuroanatomy
https://www.readbyqxmd.com/read/27913110/downregulated-brain-derived-neurotrophic-factor-induced-oxidative-stress-in-the-pathophysiology-of-diabetic-retinopathy
#19
REVIEW
Tapan Behl, Anita Kotwani
Brain-derived neurotrophic factor (BDNF), a member of neurotrophin growth factor family, physiologically mediates induction of neurogenesis and neuronal differentiation, promotes neuronal growth and survival and maintains synaptic plasticity and neuronal interconnections. Unlike the central nervous system, its secretion in the peripheral nervous system occurs in an activity-dependent manner. BDNF improves neuronal mortality, growth, differentiation and maintenance. It also provides neuroprotection against several noxious stimuli, thereby preventing neuronal damage during pathologic conditions...
November 29, 2016: Canadian Journal of Diabetes
https://www.readbyqxmd.com/read/27912762/regulation-of-effector-function-of-cns-autoreactive-cd4-t-cells-through-inhibitory-receptors-and-il-7r%C3%AE
#20
Patrick K Nuro-Gyina, Elizabeth L Rieser, Marissa C Granitto, Wei Pei, Yue Liu, Priscilla W Lee, Saba Aqel, Jian Zhang, Amy E Lovett-Racke, Michael K Racke, Yuhong Yang
BACKGROUND: Multiple sclerosis (MS) is a chronic CNS autoimmune disease characterized by inflammation, demyelination, and neuronal degeneration, where myelin-specific CD4 T cells play critical roles in the formation of acute MS lesions and disease progression. The suppression of IL-7Rα expression and the upregulation of inhibitory receptors (PD-1, etc.) are essential parts of the cell-intrinsic immunosuppressive program regulating T effector functions to prevent autoimmunity. However, little is known on the factors regulating IL-7Rα/PD-1 balance in myelin-specific CD4 T effector/memory cells during the development of CNS autoimmunity...
December 3, 2016: Journal of Neuroinflammation
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