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https://www.readbyqxmd.com/read/28212563/progression-of-motor-deficits-in-glioma-bearing-mice-impact-of-cnf1-therapy-at-symptomatic-stages
#1
Eleonora Vannini, Federica Maltese, Francesco Olimpico, Alessia Fabbri, Mario Costa, Matteo Caleo, Laura Baroncelli
Glioblastoma (GBM) is the most aggressive type of brain tumor. In this context, animal models represent excellent tools for the early detection and longitudinal mapping of neuronal dysfunction, that are critical in the preclinical validation of new therapeutic strategies. In a mouse glioma model, we developed sensitive behavioral readouts that allow early recognizing and following neurological symptoms. We injected GL261 cells into the primary motor cortex of syngenic mice and we used a battery of behavioral tests to longitudinally monitor the dysfunction induced by tumor growth...
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28212525/ablation-of-ferroptosis-regulator-glutathione-peroxidase-4-in-forebrain-neurons-promotes-cognitive-impairment-and-neurodegeneration
#2
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/28182673/the-expanded-cag-repeat-in-the-huntingtin-gene-as-target-for-therapeutic-rna-modulation-throughout-the-hd-mouse-brain
#3
Nicole A Datson, Anchel González-Barriga, Eleni Kourkouta, Rudie Weij, Jeroen van de Giessen, Susan Mulders, Outi Kontkanen, Taneli Heikkinen, Kimmo Lehtimäki, Judith C T van Deutekom
The aim of these studies was to demonstrate the therapeutic capacity of an antisense oligonucleotide with the sequence (CUG)7 targeting the expanded CAG repeat in huntingtin (HTT) mRNA in vivo in the R6/2 N-terminal fragment and Q175 knock-in Huntington's disease (HD) mouse models. In a first study, R6/2 mice received six weekly intracerebroventricular infusions with a low and high dose of (CUG)7 and were sacrificed 2 weeks later. A 15-60% reduction of both soluble and aggregated mutant HTT protein was observed in striatum, hippocampus and cortex of (CUG)7-treated mice...
2017: PloS One
https://www.readbyqxmd.com/read/28177526/segregated-fronto-cortical-and-midbrain-connections-in-the-mouse-and-their-relation-to-approach-and-avoidance-orienting-behaviors
#4
Michael Anthony Savage, Richard McQuade, Alexander Thiele
The orchestration of orienting behaviors requires the interaction of many cortical and subcortical areas, for example the Superior Colliculus (SC), as well as prefrontal areas responsible for top-down control. Orienting involves different behaviors, such as approach and avoidance. In the rat, these behaviors are at least partially mapped onto different SC subdomains, the lateral (SCl) and medial (SCm), respectively. To delineate the circuitry involved in the two types of orienting behavior in mice, we injected retrograde tracer into the intermediate and deep layers of the medial and lateral SC (SCm and SCl), and thereby determined the main input structures to these subdomains...
February 8, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28170429/cholesterol-contributes-to-dopamine-neuronal-loss-in-mptp-mouse-model-of-parkinson-s-disease-involvement-of-mitochondrial-dysfunctions-and-oxidative-stress
#5
Rajib Paul, Amarendranath Choudhury, Sanjeev Kumar, Anirudha Giri, Rajat Sandhir, Anupom Borah
Hypercholesterolemia is a known contributor to the pathogenesis of Alzheimer's disease while its role in the occurrence of Parkinson's disease (PD) is only conjecture and far from conclusive. Altered antioxidant homeostasis and mitochondrial functions are the key mechanisms in loss of dopaminergic neurons in the substantia nigra (SN) region of the midbrain in PD. Hypercholesterolemia is reported to cause oxidative stress and mitochondrial dysfunctions in the cortex and hippocampus regions of the brain in rodents...
2017: PloS One
https://www.readbyqxmd.com/read/28161373/post-onset-oral-rapamycin-treatment-delays-development-of-mitochondrial-encephalopathy-only-at-supramaximal-doses
#6
Roberta Felici, Daniela Buonvicino, Mirko Muzzi, Leonardo Cavone, Daniele Guasti, Andrea Lapucci, Sara Pratesi, Francesco De Cesaris, Francesca Luceri, Alberto Chiarugi
Mitochondrial encephalopathies are fatal, infantile neurodegenerative disorders caused by a deficit of mitochondrial functioning, for which there is urgent need to identify efficacious pharmacological treatments. Recent evidence shows that rapamycin administered both intraperitoneally or in the diet delays disease onset and enhances survival in the Ndufs4 null mouse model of mitochondrial encephalopathy. To delineate the clinical translatability of rapamycin in treatment of mitochondrial encephalopathy, we evaluated the drug's effects on disease evolution and mitochondrial parameters adopting treatment paradigms with fixed daily, oral doses starting at symptom onset in Ndufs4 knockout mice...
February 1, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28154523/effects-of-systemic-metabolic-fuels-on-glucose-and-lactate-levels-in-the-brain-extracellular-compartment-of-the-mouse
#7
Alexandria Béland-Millar, Jeremy Larcher, Justine Courtemanche, Tina Yuan, Claude Messier
Classic neuroenergetic research has emphasized the role of glucose, its transport and its metabolism in sustaining normal neural function leading to the textbook statement that it is the necessary and sole metabolic fuel of the mammalian brain. New evidence, including the Astrocyte-to-Neuron Lactate Shuttle hypothesis, suggests that the brain can use other metabolic substrates. To further study that possibility, we examined the effect of intraperitoneally administered metabolic fuels (glucose, fructose, lactate, pyruvate, ß-hydroxybutyrate, and galactose), and insulin, on blood, and extracellular brain levels of glucose and lactate in the adult male CD1 mouse...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28137974/an-ultrastructural-study-of-the-thalamic-input-to-layer-4-of-primary-motor-and-primary-somatosensory-cortex-in-the-mouse
#8
Rita Bopp, Simone Holler-Rickauer, Kevan A C Martin, Gregor F P Schuhknecht
: The traditional classification of primary motor cortex (M1) as an agranular area has recently been challenged, when a functional layer 4 (L4) was reported in M1. L4 is the principal target for thalamic input in sensory areas, which raises the question how thalamocortical synapses formed in M1 in the mouse compare with those in neighboring sensory cortex (S1). We identified thalamic boutons by their immunoreactivity for the vesicular glutamate transporter 2 (VGluT2) and performed unbiased disector counts from electron micrographs...
January 30, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28131769/suppression-of-inhibitory-g-protein-signaling-in-forebrain-pyramidal-neurons-triggers-plasticity-of-glutamatergic-neurotransmission-in-the-nucleus-accumbens-core
#9
Ezequiel Marron Fernandez de Velasco, Nicholas Carlblom, Zhilian Xia, Kevin Wickman
Cocaine and other drugs of abuse trigger long-lasting adaptations in excitatory and inhibitory neurotransmission in the mesocorticolimbic system, and this plasticity has been implicated in several key facets of drug addiction. For example, glutamatergic neurotransmission mediated by AMPA receptors (AMPAR) is strengthened in medium spiny neurons (MSNs) in the NAc core and shell during withdrawal following repeated in vivo cocaine administration. Repeated cocaine administration also suppresses inhibitory signaling mediated by G protein-gated inwardly rectifying K(+) (GIRK) channels in pyramidal neurons of the prelimbic cortex, an important source of glutamatergic input to the NAc core that has been implicated in cocaine-seeking and behavioral sensitization...
January 25, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28119822/gene-therapy-for-a-mouse-model-of-glucose-transporter-1-deficiency-syndrome
#10
Sachie Nakamura, Hitoshi Osaka, Shin-Ichi Muramatsu, Naomi Takino, Mika Ito, Shiho Aoki, Eriko F Jimbo, Kuniko Shimazaki, Tatsushi Onaka, Sumio Ohtsuki, Tetsuya Terasaki, Takanori Yamagata
OBJECTIVE: We generated an adeno-associated virus (AAV) vector in which the human SLC2A1 gene was expressed under the synapsin I promoter (AAV-hSLC2A1) and examined if AAV-hSLC2A1 administration can lead to functional improvement in GLUT1-deficient mice. METHODS: AAV-hSLC2A1 was injected into heterozygous knock-out murine Glut1 (GLUT1(+/-)) mice intraperitoneally (systemic; 1.85 × 10(11) vg/mouse) or intra-cerebroventricularly (local; 1.85 × 10(10) vg/mouse)...
March 2017: Molecular Genetics and Metabolism Reports
https://www.readbyqxmd.com/read/28108555/immune-dysregulation-may-contribute-to-disease-pathogenesis-in-spinal-muscular-atrophy-mice
#11
Marc-Olivier Deguise, Yves De Repentigny, Emily McFall, Nicole Auclair, Subash Sad, Rashmi Kothary
Spinal muscular atrophy (SMA) has long been solely considered a neurodegenerative disorder. However, recent work has highlighted defects in many other cell types that could contribute to disease aetiology. Interestingly, the immune system has never been extensively studied in SMA. Defects in lymphoid organs could exacerbate disease progression by neuroinflammation or immunodeficiency. Smn depletion led to severe alterations in the thymus and spleen of two different mouse models of SMA. The spleen from Smn depleted mice was dramatically smaller at a very young age and its histological architecture was marked by mislocalization of immune cells in the Smn(2B/-) model mice...
January 19, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28099507/correlations-of-behavioral-deficits-with-brain-pathology-assessed-through-longitudinal-mri-and-histopathology-in-the-hdhq150-q150-mouse-model-of-huntington-s-disease
#12
Ivan Rattray, Edward J Smith, William R Crum, Thomas A Walker, Richard Gale, Gillian P Bates, Michel Modo
A variety of mouse models have been developed that express mutant huntingtin (mHTT) leading to aggregates and inclusions that model the molecular pathology observed in Huntington's disease. Here we show that although homozygous HdhQ150 knock-in mice developed motor impairments (rotarod, locomotor activity, grip strength) by 36 weeks of age, cognitive dysfunction (swimming T maze, fear conditioning, odor discrimination, social interaction) was not evident by 94 weeks. Concomitant to behavioral assessments, T2-weighted MRI volume measurements indicated a slower striatal growth with a significant difference between wild type (WT) and HdhQ150 mice being present even at 15 weeks...
2017: PloS One
https://www.readbyqxmd.com/read/28092659/rem-sleep-selectively-prunes-and-maintains-new-synapses-in-development-and-learning
#13
Wei Li, Lei Ma, Guang Yang, Wen-Biao Gan
The functions and underlying mechanisms of rapid eye movement (REM) sleep remain unclear. Here we show that REM sleep prunes newly formed postsynaptic dendritic spines of layer 5 pyramidal neurons in the mouse motor cortex during development and motor learning. This REM sleep-dependent elimination of new spines facilitates subsequent spine formation during development and when a new motor task is learned, indicating a role for REM sleep in pruning to balance the number of new spines formed over time. Moreover, REM sleep also strengthens and maintains newly formed spines, which are critical for neuronal circuit development and behavioral improvement after learning...
January 16, 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28087762/a-delay-between-motor-cortex-lesions-and-neuronal-transplantation-enhances-graft-integration-and-improves-repair-and-recovery
#14
Sophie Péron, Marine Droguerre, Franck Debarbieux, Nissrine Ballout, Marianne Benoit-Marand, Maureen Francheteau, Sébastien Brot, Geneviève Rougon, Mohamed Jaber, Afsaneh Gaillard
We previously reported that embryonic motor cortical neurons transplanted immediately after lesions in the adult mouse motor cortex restored damaged motor cortical pathways. A critical barrier hindering application of transplantation strategies for a wide range of traumatic injuries is the determination of a suitable time window for therapeutic intervention. Here, we report that a one-week delay between the lesion and transplantation significantly enhances graft vascularization, survival and proliferation of grafted cells...
January 13, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28072877/motor-cortex-theta-and-gamma-architecture-in-young-adult-appsweps1de9-alzheimer-mice
#15
Anna Papazoglou, Julien Soos, Andreas Lundt, Carola Wormuth, Varun Raj Ginde, Ralf Müller, Christina Henseler, Karl Broich, Kan Xie, Britta Haenisch, Dan Ehninger, Marco Weiergräber
Alzheimer's disease (AD) is a multifactorial disorder leading to progressive memory loss and eventually death. In this study, an APPswePS1dE9 AD mouse model has been analyzed for motor cortex theta, beta and gamma frequency alterations using computerized 3D stereotaxic electrode positioning and implantable video-EEG radiotelemetry to perform long-term M1 recordings from both genders considering age, circadian rhythm and activity status of experimental animals. We previously demonstrated that APPswePS1dE9 mice exibit complex alterations in hippocampal frequency power and another recent investigation reported a global increase of alpha, beta and gamma power in APPswePS1dE9 in females of 16-17 weeks of age...
2017: PloS One
https://www.readbyqxmd.com/read/28057929/a-novel-role-for-the-dna-repair-gene-rad51-in-netrin-1-signalling
#16
K A Glendining, D Markie, R J M Gardner, E A Franz, S P Robertson, C L Jasoni
Mutations in RAD51 have recently been linked to human Congenital Mirror Movements (CMM), a developmental disorder of the motor system. The only gene previously linked to CMM encodes the Netrin-1 receptor DCC, which is important for formation of corticospinal and callosal axon tracts. Thus, we hypothesised that Rad51 has a novel role in Netrin-1-mediated axon development. In mouse primary motor cortex neurons, Rad51 protein was redistributed distally down the axon in response to Netrin-1, further suggesting a functional link between the two...
January 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28032120/inhibition-of-poly-adp-ribosylation-fails-to-increase-axonal-regeneration-or-improve-functional-recovery-after-adult-mammalian-cns-injury
#17
Xingxing Wang, Yuichi Sekine, Alexandra B Byrne, William B J Cafferty, Marc Hammarlund, Stephen M Strittmatter
After traumatic damage of the brain or spinal cord, many surviving neurons are disconnected, and recovery of function is limited by poor axon regeneration. Recent data have suggested that poly ADP-ribosylation plays a role in limiting axonal regrowth such that inhibition of poly (ADP-ribose) polymerase (PARP) may have therapeutic efficacy for neurological recovery after trauma. Here, we tested systemic administration of the PARP inhibitor, veliparib, and showed effective suppression of PARylation in the mouse CNS...
November 2016: ENeuro
https://www.readbyqxmd.com/read/28030474/therapeutic-benefits-of-the-methyl-donor-s-adenosylmethionine-sam-on-nerve-injury-induced-mechanical-hypersensitivity-and-cognitive-impairment-in-mice
#18
Stéphanie Grégoire, Magali Millecamps, Lina Naso, Sonia Do Carmo, A Claudio Cuello, Moshe Szyf, Laura S Stone
Despite considerable advances in understanding mechanisms involved in chronic pain, effective treatment remains elusive. Co-morbid conditions including anxiety, depression and cognitive impairment further impact quality of life. Chronic pain is associated with reversible changes in brain anatomy and function and with long-term changes in gene expression. Epigenetic mechanisms, including DNA methylation, contribute to wide-spread and long-lasting reprogramming of gene expression. We previously reported decreases in global DNA methylation in the mouse frontal cortex six months following induction of neuropathic pain using the Spared Nerve Injury (SNI) model...
December 22, 2016: Pain
https://www.readbyqxmd.com/read/28018170/mrna-transcriptomics-of-galectins-unveils-heterogeneous-organization-in-mouse-and-human-brain
#19
Sebastian John, Rashmi Mishra
Background: Galectins, a family of non-classically secreted, β-galactoside binding proteins is involved in several brain disorders; however, no systematic knowledge on the normal neuroanatomical distribution and functions of galectins exits. Hence, the major purpose of this study was to understand spatial distribution and predict functions of galectins in brain and also compare the degree of conservation vs. divergence between mouse and human species. The latter objective was required to determine the relevance and appropriateness of studying galectins in mouse brain which may ultimately enable us to extrapolate the findings to human brain physiology and pathologies...
2016: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28009277/movement-initiation-signals-in-mouse-whisker-motor-cortex
#20
Varun Sreenivasan, Vahid Esmaeili, Taro Kiritani, Katia Galan, Sylvain Crochet, Carl C H Petersen
Frontal cortex plays a central role in the control of voluntary movements, which are typically guided by sensory input. Here, we investigate the function of mouse whisker primary motor cortex (wM1), a frontal region defined by dense innervation from whisker primary somatosensory cortex (wS1). Optogenetic stimulation of wM1 evokes rhythmic whisker protraction (whisking), whereas optogenetic inactivation of wM1 suppresses initiation of whisking. Whole-cell membrane potential recordings and silicon probe recordings of action potentials reveal layer-specific neuronal activity in wM1 at movement initiation, and encoding of fast and slow parameters of movements during whisking...
December 21, 2016: Neuron
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