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https://www.readbyqxmd.com/read/29214257/piceatannol-attenuates-behavioral-disorder-and-neurological-deficits-in-aging-mice-via-activating-the-nrf2-pathway
#1
Yan Zhang, Li-Hong Zhang, Xi Chen, Ning Zhang, Guang Li
Aging is a complex process that is accompanied by neurological damage. Chronic injection of d-galactose (d-gal) can accelerate the aging process similar to natural aging and is commonly used to build an aging model to investigate aging. In the present study, the effects of piceatannol on d-gal-induced aging in mice were evaluated. Piceatannol treatment showed an observable anti-aging effect. Results obtained in vivo showed that piceatannol retained spontaneous motor activity and enhanced spatial learning and memory abilities in mice in which aging was induced by d-gal...
December 7, 2017: Food & Function
https://www.readbyqxmd.com/read/29196686/resting-state-functional-mri-reveals-altered-brain-connectivity-and-its-correlation-with-motor-dysfunction-in-a-mouse-model-of-huntington-s-disease
#2
Qiang Li, Gang Li, Dan Wu, Hanbing Lu, Zhipeng Hou, Christopher A Ross, Yihong Yang, Jiangyang Zhang, Wenzhen Duan
Huntington's disease (HD) is an autosomal dominant inherited neurodegenerative disorder, and no cure is available currently. Treatment of HD is likely to be most beneficial in the early, possibly pre-manifestation stage. The challenge is to determine the best time for intervention and evaluate putative efficacy in the absence of clinical symptoms. Resting-state functional MRI may represent a promising tool to develop biomarker reflecting early neuronal dysfunction in HD brain, because it can examine multiple brain networks without confounding effects of cognitive ability, which makes the resting-state fMRI promising as a translational bridge between preclinical study in animal models and clinical findings in HD patients...
December 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29192125/endocannabinoid-specific-impairment-in-synaptic-plasticity-in-striatum-of-huntington-s-disease-mouse-model
#3
Marja D Sepers, Amy Smith-Dijak, Jeff LeDue, Karolina Kolodziejczyk, Ken Mackie, Lynn A Raymond
Huntington's disease (HD) is an inherited neurodegenerative disease affecting predominantly striatum and cortex that results in motor and cognitive disorders. Prior to a motor phenotype, animal models of HD show aberrant cortical-striatal glutamate signaling. Here, we tested synaptic plasticity of cortical excitatory synapses onto striatal spiny projection neurons (SPNs) early in the YAC128 mouse model of HD. High frequency stimulation-induced long-term depression, mediated by the endocannabinoid anandamide and cannabinoid receptor 1 (CB1), was significantly attenuated in male and female YAC128 SPNs...
November 30, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29184069/phosphorylated-exogenous-alpha-synuclein-fibrils-exacerbate-pathology-and-induce-neuronal-dysfunction-in-mice
#4
Mantia Karampetsou, Mustafa T Ardah, Maria Semitekolou, Alexia Polissidis, Martina Samiotaki, Maria Kalomoiri, Nour Majbour, Georgina Xanthou, Omar M A El-Agnaf, Kostas Vekrellis
Approximately 90% of alpha-synuclein (α-Synuclein) deposited in Lewy bodies is phosphorylated at serine 129 suggesting that the accumulation of phosphorylated α-Synuclein is critical in the pathogenesis of Parkinson's disease. However, in vivo experiments addressing the role of phosphorylated α-Synuclein in the progression of Parkinson's disease have produced equivocal data. To clarify a role of Ser129 phosphorylation of α-Synuclein in pathology progression we performed stereotaxic injections targeting the mouse striatum with three fibrilar α-Synuclein types: wt-fibrils, phosphorylated S129 fibrils and, phosphorylation incompetent, S129A fibrils...
November 28, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29180135/alpha-synuclein-transgenic-mice-h-%C3%AE-synl62-display-%C3%AE-syn-aggregation-and-a-dopaminergic-phenotype-reminiscent-of-parkinson-s-disease
#5
Silke Frahm, Valeria Melis, David Horsley, Janet E Rickard, Gernot Riedel, Paula Fadda, Maria Scherma, Charles R Harrington, Claude M Wischik, Franz Theuring, Karima Schwab
Alpha-Synuclein (α-Syn) accumulation is considered a major risk factor for the development of synucleinopathies such as Parkinson's disease (PD) and dementia with Lewy bodies. We have generated mice overexpressing full-length human α-Syn fused to a membrane-targeting signal sequence under the control of the mouse Thy1-promotor. Three separate lines (L56, L58 and L62) with similar gene expression levels, but considerably heightened protein accumulation in L58 and L62, were established. In L62, there was widespread labelling of α-Syn immunoreactivity in brain including spinal cord, basal forebrain, cortex and striatum...
November 24, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/29175956/the-mouse-pulvinar-nucleus-links-the-lateral-extrastriate-cortex-striatum-and-amygdala
#6
N Zhou, S P Masterson, J K Damron, W Guido, M E Bickford
The pulvinar nucleus is a large thalamic structure involved in the integration of visual and motor signals. The pulvinar forms extensive connections with striate and extrastriate cortical areas, but the impact of these connections on cortical circuits has not previously been directly tested. Using a variety of anatomical, optogenetic, and in vitro physiological techniques in male and female mice, we show that pulvinocortical terminals are densely distributed in the extrastriate cortex where they form synaptic connections with spines and small diameter dendrites...
November 23, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29156684/a-prenatal-interruption-of-disc1-function-in-the-brain-exhibits-a-lasting-impact-on-adult-behaviors-brain-metabolism-and-interneuron-development
#7
Dazhi Deng, Chongdong Jian, Ling Lei, Yijing Zhou, Colleen McSweeney, Fengping Dong, Yilun Shen, Donghua Zou, Yonggang Wang, Yuan Wu, Limin Zhang, Yingwei Mao
Mental illnesses like schizophrenia (SCZ) and major depression disorder (MDD) are devastating brain disorders. The SCZ risk gene, disrupted in schizophrenia 1 (DISC1), has been associated with neuropsychiatric conditions. However, little is known regarding the long-lasting impacts on brain metabolism and behavioral outcomes from genetic insults on fetal NPCs during early life. We have established a new mouse model that specifically interrupts DISC1 functions in NPCs in vivo by a dominant-negative DISC1 (DN-DISC1) with a precise temporal and spatial regulation...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29154281/gradual-cerebral-hypoperfusion-impairs-fear-conditioning-and-object-recognition-learning-and-memory-in-mice-potential-roles-of-neurodegeneration-and-cholinergic-dysfunction
#8
Jogender Mehla, Sean Lacoursiere, Emily Stuart, Robert J McDonald, Majid H Mohajerani
In the present study, male C57BL/6J mice were subjected to gradual cerebral hypoperfusion by implanting an ameroid constrictor (AC) on the left common carotid artery (CCA) and a stenosis on the right CCA. In the sham group, all surgical procedures were kept the same except no AC was implanted and stenosis was not performed. One month following the surgical procedures, fear conditioning and object recognition tests were conducted to evaluate learning and memory functions and motor functions were assessed using a balance beam test...
November 14, 2017: Journal of Alzheimer's Disease: JAD
https://www.readbyqxmd.com/read/29137651/abnormal-dendritic-calcium-activity-and-synaptic-depotentiation-occur-early-in-a-mouse-model-of-alzheimer-s-disease
#9
Yang Bai, Miao Li, Yanmei Zhou, Lei Ma, Qian Qiao, Wanling Hu, Wei Li, Zachary Patrick Wills, Wen-Biao Gan
BACKGROUND: Alzheimer's disease (AD) is characterized by amyloid deposition, tangle formation as well as synapse loss. Synaptic abnormalities occur early in the pathogenesis of AD. Identifying early synaptic abnormalities and their underlying mechanisms is likely important for the prevention and treatment of AD. METHODS: We performed in vivo two-photon calcium imaging to examine the activities of somas, dendrites and dendritic spines of layer 2/3 pyramidal neurons in the primary motor cortex in the APPswe/PS1dE9 mouse model of AD and age-matched wild type control mice...
November 14, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/29133437/abnormal-microglia-and-enhanced-inflammation-related-gene-transcription-in-mice-with-conditional-deletion-of-ctcf-in-camk2a-cre-expressing-neurons
#10
Bryan E McGill, Ruteja A Barve, Susan E Maloney, Amy Strickland, Nicholas Rensing, Peter Wang, Michael Wong, Richard Head, David F Wozniak, Jeffrey Milbrandt
CCCTC-binding factor (CTCF) is an 11 zinc finger DNA-binding domain protein that regulates gene expression by modifying three dimensional chromatin structure. Human mutations in CTCF cause intellectual disability and autistic features. Knocking out Ctcf in mouse embryonic neurons is lethal by neonatal age, but the effects of CTCF deficiency in postnatal neurons are less well studied. We knocked out Ctcf postnatally in glutamatergic forebrain neurons under the control of Camk2a-CreCtcfloxP/loxP ;Camk2a-Cre+ (Ctcf CKO) mice of both sexes were viable and exhibited profound deficits in spatial learning/memory, impaired motor co-ordination, and decreased sociability by 4 months of age...
November 13, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29126932/docosahexaenoic-acid-dha-enhances-the-therapeutic-potential-of-neonatal-neural-stem-cell-transplantation-post-traumatic-brain-injury
#11
Hussein Ghazale, Naify Ramadan, Sara Mantash, Kazem Zibara, Sally El-Sitt, Hala Darwish, Farah Chamaa, Rose Mary Boustany, Stefania Mondello, Wassim Abou-Kheir, Jihane Soueid, Firas Kobeissy
Traumatic Brain Injury (TBI) is a major cause of death and disability worldwide with 1.5 million people inflicted yearly. Several neurotherapeutic interventions have been proposed including drug administration as well as cellular therapy involving neural stem cells (NSCs). Among the proposed drugs is docosahexaenoic acid (DHA), a polyunsaturated fatty acid, exhibiting neuroprotective properties. In this study, we utilized an innovative intervention of neonatal NSCs transplantation in combination with DHA injections in order to ameliorate brain damage and promote functional recovery in an experimental model of TBI...
November 7, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/29101523/functional-comparison-of-corticostriatal-and-thalamostriatal-postsynaptic-responses-in-striatal-neurons-of-the-mouse
#12
M A Arias-García, D Tapia, J A Laville, V M Calderón, Y Ramiro-Cortés, J Bargas, E Galarraga
Synaptic inputs from cortex and thalamus were compared in electrophysiologically defined striatal cell classes: direct and indirect pathways' striatal projection neurons (dSPNs and iSPNs), fast-spiking interneurons (FS), cholinergic interneurons (ChINs), and low-threshold spiking-like (LTS-like) interneurons. Our purpose was to observe whether stimulus from cortex or thalamus had equivalent synaptic strength to evoke prolonged suprathreshold synaptic responses in these neuron classes. Subthreshold responses showed that inputs from either source functionally mix up in their dendrites at similar electrotonic distances from their somata...
November 3, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/29079747/disulfide-cross-linked-multimers-of-tdp-43-and-spinal-motoneuron%C3%A2-loss-in-a-tdp-43-a315t-als-ftd-mouse-model
#13
Leslie Bargsted, Danilo B Medinas, Francisca Martínez Traub, Pablo Rozas, Natalia Muñoz, Melissa Nassif, Carolina Jerez, Alejandra Catenaccio, Felipe A Court, Claudio Hetz, Soledad Matus
Tar DNA binding protein 43 (TDP-43) is the principal component of ubiquitinated protein inclusions present in nervous tissue of most cases of both amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Previous studies described a TDP-43(A315T) transgenic mouse model that develops progressive motor dysfunction in the absence of protein aggregation or significant motoneuron loss, questioning its validity to study ALS. Here we have further characterized the course of the disease in TDP-43(A315T) mice using a battery of tests and biochemical approaches...
October 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29074463/disruption-of-at-hook-1-domain-in-mecp2-protein-caused-behavioral-abnormality-in-mice
#14
Miaojing Xu, Pingping Song, Wei Huang, Rongni He, Yong He, Xiao Zhou, Yong Gu, Suyue Pan, Yafang Hu
MECP2 is the causative gene for autism spectrum disorders, including Rett syndrome, a regressive neurodevelopmental rare disease mainly occurring in girls. Except for the distinct methyl-CpG binding domain and the transcriptional repression domain in MeCP2, three AT-hook-like domains have recently been identified. Several mutations in AT-hook 1 domain have been reported in autism cases or Rett database. However, the role of AT-hook 1 domain is still unclear. In this study, we generated a mouse line carrying deletion of eight conserved amino acids in AT-hook 1 domain by clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 technology...
October 24, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29060072/localization-of-ultrasound-waveform-for-low-intensity-ultrasound-induced-neuromodulation-in-a-mouse-model
#15
Kang-Il Song, Seul Lee, Sunghee E Park, Dosik Hwang, Hyungmin Kim, Inchan Youn
A collimator design was investigated to localize ultrasound stimulation using a flat ultrasound transducer for ultrasound-induced neuromodulation in a mouse model. In brain stimulation, the specific location of stimulation must be specified, as the region responsible for motor or sensory function is clustered in a narrow brain area. To localize ultrasound stimulation, three types of collimator design were simulated to determine the optimal collimator design. The performance of the simulated optimal collimator was compared to that of an unmounted collimator in a transducer in both in vivo and in vitro experiments...
July 2017: Conference Proceedings: Annual International Conference of the IEEE Engineering in Medicine and Biology Society
https://www.readbyqxmd.com/read/29038583/zdhhc13-dependent-drp1-s-palmitoylation-impacts-brain-bioenergetics-anxiety-coordination-and-motor-skills
#16
Eleonora Napoli, Gyu Song, Siming Liu, Alexsandra Espejo, Carlos J Perez, Fernando Benavides, Cecilia Giulivi
Protein S-palmitoylation is a reversible post-translational modification mediated by palmitoyl acyltransferase enzymes, a group of Zn(2+)-finger DHHC-domain-containing proteins (ZDHHC). Here, for the first time, we show that Zdhhc13 plays a key role in anxiety-related behaviors and motor function, as well as brain bioenergetics, in a mouse model (luc) carrying a spontaneous Zdhhc13 recessive mutation. At 3 m of age, mutant mice displayed increased sensorimotor gating, anxiety, hypoactivity, and decreased motor coordination, compared to littermate controls...
October 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29033800/stimulation-of-cortico-subthalamic-projections-amplifies-resting-motor-circuit-activity-and-leads-to-increased-locomotion-in-dopamine-depleted-mice
#17
Teresa H Sanders
Deep brain stimulation (DBS) of the subthalamic nucleus (STN) improves motor function in patients with Parkinson's disease (PD). STN-DBS enables similar improved motor function, including increased movement speed (reduced bradykinesia), in the 6-OHDA dopamine-depletion mouse model of PD. Previous analyses of electrophysiological recordings from STN and motor cortex (M1) have explored signaling changes that correspond to PD and amelioration of PD symptoms. The most common results show an increase in beta frequency power during 'off' states and a reduction in beta during 'on' states...
2017: Frontiers in Integrative Neuroscience
https://www.readbyqxmd.com/read/29020619/remarkable-stability-of-myelinating-oligodendrocytes-in-mice
#18
Richa B Tripathi, Martyna Jackiewicz, Ian A McKenzie, Eleni Kougioumtzidou, Matthew Grist, William D Richardson
New myelin-forming oligodendrocytes (OLs) are generated in the mouse central nervous system during adulthood. These adult-born OLs might augment the existing population, contributing to neural plasticity, or else replace OLs that die in use (turnover). To distinguish between these alternatives, we induced genetic labeling of mature myelinating OLs in young adult mice and tracked their subsequent survival. OL survival rates were region dependent, being higher in corpus callosum (∼90% survival over 20 months) and motor cortex (∼70% survival) than in corticospinal tract or optic nerve (50%-60% survival)...
October 10, 2017: Cell Reports
https://www.readbyqxmd.com/read/28945191/two-photon-calcium-imaging-of-the-medial-prefrontal-cortex-and-hippocampus-without-cortical-invasion
#19
Masashi Kondo, Kenta Kobayashi, Masamichi Ohkura, Junichi Nakai, Masanori Matsuzaki
In vivo two-photon calcium imaging currently allows us to observe the activity of multiple neurons up to ~900 µm below the cortical surface without cortical invasion. However, many important brain areas are located deeper than this. Here, we used an 1100 nm laser that underfilled the back aperture of the objective together with red genetically encoded calcium indicators to establish two-photon calcium imaging of the intact mouse brain and detect neural activity up to 1200 μm from the cortical surface. This imaging was obtained from the medial prefrontal cortex (the prelimbic area) and the hippocampal CA1 region...
September 25, 2017: ELife
https://www.readbyqxmd.com/read/28941811/reversible-induction-of-tdp-43-granules-in-cortical-neurons-after-traumatic-injury
#20
Diana Wiesner, Lilla Tar, Birgit Linkus, Akila Chandrasekar, Florian Olde Heuvel, Luc Dupuis, William Tsao, Philip C Wong, Albert Ludolph, Francesco Roselli
Traumatic brain injury (TBI) has been proposed as a risk factor for neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). To determine whether TBI might trigger or exacerbate ALS-relevant pathology, we delivered a mild stab-wound injury to the motor cortex of three different ALS mouse models expressing mutations in SOD1, TDP-43 or FUS and scrutinized the effects on the formation of phospho-TDP-43 (pTDP-43) cytoplasmic granules. Stab-injury induced the formation of cytoplasmic TDP-43 granules in wt animals, peaking at 3dpi; a much larger response was seen in mutant TDP-43 mice, whose response peaked at 7dpi...
September 21, 2017: Experimental Neurology
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