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https://www.readbyqxmd.com/read/28424060/effects-of-a-combination-treatment-of-kd5040-and-l-dopa-in-a-mouse-model-of-parkinson-s-disease
#1
Sora Ahn, Taek-Jin Song, Seong-Uk Park, Songhee Jeon, Jongpil Kim, Joo-Young Oh, Jaehwan Jang, Sanhwa Hong, Min-A Song, Hye-Seoung Shin, Young-Rim Jung, Hi-Joon Park
BACKGROUND: Although the dopamine precursor L-3, 4-dihydroxyphenylalanine ( l -dopa) remains the gold standard pharmacological therapy for patients with Parkinson's disease (PD), long-term treatment with this drug has been known to result in several adverse effects, including l -dopa-induced dyskinesia (LID). Recently, our group reported that KD5040, a modified herbal remedy, had neuroprotective effects in both in vitro and in vivo models of PD. Thus, the present study investigated whether KD5040 would have synergistic effects with l -dopa and antidyskinetic effects caused by l -dopa as well...
April 19, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28412497/optogenetic-stimulation-of-cortex-to-map-evoked-whisker-movements-in-awake-head-restrained-mice
#2
Matthieu Auffret, Veronica L Ravano, Giulia M C Rossi, Nicolas Hankov, Merissa F A Petersen, Carl C H Petersen
Whisker movements are used by rodents to touch objects in order to extract spatial and textural tactile information about their immediate surroundings. To understand the mechanisms of such active sensorimotor processing it is important to investigate whisker motor control. The activity of neurons in the neocortex affects whisker movements, but many aspects of the organization of cortical whisker motor control remain unknown. Here, we filmed whisker movements evoked by sequential optogenetic stimulation of different locations across the left dorsal sensorimotor cortex of awake head-restrained mice...
April 12, 2017: Neuroscience
https://www.readbyqxmd.com/read/28411148/behavioural-characterization-of-ankyring-deficient-mice-a-model-for-ank3-related-disorders
#3
I M van der Werf, D Van Dam, S Missault, B Yalcin, P P De Deyn, G Vandeweyer, R F Kooy
ANK3 encodes AnkyrinG (AnkG), a member of the Ankyrin family that is expressed in several different isoforms in many tissues. A unique serine-rich domain and tail domain in the two largest isoforms of AnkG (270 and 480kDa), restrict AnkG to the axon initial segment and nodes of Ranvier of myelinated neurons. At these sites, AnkG is a master regulator, coordinating the strict clustering of components necessary for proper action potential initiation and propagation along the axon. These components include voltage-gated sodium channels, potassium channels and members of the L1 cell adhesion molecule family...
April 11, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28396257/b-vitamin-and-choline-supplementation-increases-neuroplasticity-and-recovery-after-stroke
#4
Nafisa M Jadavji, Joshua T Emmerson, Amanda J MacFarlane, William G Willmore, Patrice D Smith
Folates are B-vitamins that play an important role in brain function. Dietary and genetic deficiencies in folate metabolism result in elevated levels of homocysteine which have been linked to increased risk of developing a stroke. Reducing levels of homocysteine before or after a stroke through B-vitamin supplementation has been a focus of many clinical studies, however, the results remain inconsistent. Animal model systems provide a powerful mechanism to study and understand functional impact and mechanisms through which supplementation affects stroke recovery...
April 7, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28388629/a-tubulin-alpha-8-mouse-knockout-model-indicates-a-likely-role-in-spermatogenesis-but-not-in-brain-development
#5
Christine P Diggle, Isabel Martinez-Garay, Zoltan Molnar, Martin H Brinkworth, Ed White, Ewan Fowler, Ruth Hughes, Bruce E Hayward, Ian M Carr, Christopher M Watson, Laura Crinnion, Aruna Asipu, Ben Woodman, P Louise Coletta, Alexander F Markham, T Neil Dear, David T Bonthron, Michelle Peckham, Ewan E Morrison, Eamonn Sheridan
Tubulin alpha 8 (Tuba8) is the most divergent member of the highly conserved alpha tubulin family, and uniquely lacks two key post-translational modification sites. It is abundantly expressed in testis and muscle, with lower levels in the brain. We previously identified homozygous hypomorphic TUBA8 mutations in human subjects with a polymicrogyria (PMG) syndrome, suggesting its involvement in development of the cerebral cortex. We have now generated and characterized a Tuba8 knockout mouse model. Homozygous mice were confirmed to lack Tuba8 protein in the testis, but did not display PMG and appeared to be neurologically normal...
2017: PloS One
https://www.readbyqxmd.com/read/28379350/primary-auditory-cortex-is-required-for-anticipatory-motor-response
#6
Jingcheng Li, Xiang Liao, Jianxiong Zhang, Meng Wang, Nian Yang, Jun Zhang, Guanghui Lv, Haohong Li, Jian Lu, Ran Ding, Xingyi Li, Yu Guang, Zhiqi Yang, Han Qin, Wenjun Jin, Kuan Zhang, Chao He, Hongbo Jia, Shaoqun Zeng, Zhian Hu, Israel Nelken, Xiaowei Chen
The ability of the brain to predict future events based on the pattern of recent sensory experience is critical for guiding animal's behavior. Neocortical circuits for ongoing processing of sensory stimuli are extensively studied, but their contributions to the anticipation of upcoming sensory stimuli remain less understood. We, therefore, used in vivo cellular imaging and fiber photometry to record mouse primary auditory cortex to elucidate its role in processing anticipated stimulation. We found neuronal ensembles in layers 2/3, 4, and 5 which were activated in relationship to anticipated sound events following rhythmic stimulation...
April 4, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28351750/a-longitudinal-dti-and-histological-study-of-the-spinal-cord-reveals-early-pathological-alterations-in-g93a-sod1-mouse-model-of-amyotrophic-lateral-sclerosis
#7
Stefania Marcuzzo, Silvia Bonanno, Matteo Figini, Alessandro Scotti, Ileana Zucca, Ludovico Minati, Nilo Riva, Teuta Domi, Andrea Fossaghi, Angelo Quattrini, Barbara Galbardi, Sara D'Alessandro, Maria Grazia Bruzzone, José Manuel García-Verdugo, Victoria Moreno-Manzano, Renato Mantegazza, Pia Bernasconi
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by selective motor neuron degeneration in the motor cortex, brainstem and spinal cord. It is generally accepted that ALS is caused by death of motor neurons, however the exact temporal cascade of degenerative processes is not yet completely known. To identify the early pathological changes in spinal cord of G93A-SOD1 ALS mice we performed a comprehensive longitudinal analysis employing diffusion-tensor magnetic resonance imaging alongside histology and electron microscopy, in parallel with peripheral nerve histology...
March 27, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28348649/down-regulated-expression-of-aquaporin-4-in-the-cerebellum-after-status-epilepticus
#8
Hui Tang, Chuan Shao, Jiaquan He
Status epilepticus (SE) is a common neurological condition associated with high rates of mortality and permanent brain injury. SE usually leads to neuronal death which may be accompanied by edema, epileptogenesis and learning impairment. Aquaporin-4 (AQP4), is a transmembrane water channel protein in the neuropil of the central nervous system that has an important role in water transport in the brain; AQP4 expression is altered in many pathological conditions such as changes in the blood- brain barrier and/or astrocytic activation, including seizures...
April 2017: Cognitive Neurodynamics
https://www.readbyqxmd.com/read/28343366/motor-learning-in-animal-models-of-parkinson-s-disease-aberrant-synaptic-plasticity-in-the-motor-cortex
#9
REVIEW
Tonghui Xu, Shaofang Wang, Rupa R Lalchandani, Jun B Ding
In Parkinson's disease (PD), dopamine depletion causes major changes in the brain, resulting in the typical cardinal motor features of the disease. PD neuropathology has been restricted to postmortem examinations, which are limited to only a single time of PD progression. Models of PD in which dopamine tone in the brain is chemically or physically disrupted are valuable tools in understanding the mechanisms of the disease. The basal ganglia have been well studied in the context of PD, and circuit changes in response to dopamine loss have been linked to the motor dysfunctions in PD...
April 2017: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/28334611/somatosensory-cortex-plays-an-essential-role-in-forelimb-motor-adaptation-in-mice
#10
Mackenzie Weygandt Mathis, Alexander Mathis, Naoshige Uchida
Our motor outputs are constantly re-calibrated to adapt to systematic perturbations. This motor adaptation is thought to depend on the ability to form a memory of a systematic perturbation, often called an internal model. However, the mechanisms underlying the formation, storage, and expression of such models remain unknown. Here, we developed a mouse model to study forelimb adaptation to force field perturbations. We found that temporally precise photoinhibition of somatosensory cortex (S1) applied concurrently with the force field abolished the ability to update subsequent motor commands needed to reduce motor errors...
March 22, 2017: Neuron
https://www.readbyqxmd.com/read/28315945/organization-of-the-reach-and-grasp-in-head-fixed-vs-freely-moving-mice-provides-support-for-multiple-motor-channel-theory-of-neocortical-organization
#11
Ian Q Whishaw, Jamshid Faraji, Jessica Kuntz, Behroo Mirza Agha, Mukt Patel, Gerlinde A S Metz, Majid H Mohajerani
Multiple motor channel (MMC) theory of neocortical organization proposes that complex movements, such as reaching for a food item to eat, are produced by the coordinated action of separate neural channels. For example, the human reach-to-grasp act is mediated by two visuo-parieto-motor cortex channels, one for the reach and one for the grasp. The present analysis asked whether there is a similar organization of reach-and-grasp movements in the mouse. The reach-to-eat movements of the same mice were examined from high-shutter speed, frame-by-frame video analysis in three tasks in which the mice obtained equivalent success scores: when freely-moving reaching for food pellets, when head-fixed reaching for food pellets, and when head-fixed reaching for pieces of pasta...
March 18, 2017: Experimental Brain Research. Experimentelle Hirnforschung. Expérimentation Cérébrale
https://www.readbyqxmd.com/read/28315294/neuronal-cell-sheet-of-cortical-motor-neuron-phenotype-derived-from-human-ips-cells
#12
Noboru Suzuki, Nagisa Arimitsu, Jun Shimizu, Kenji Takai, Chieko Hirotsu, Erika Takada, Yuji Ueda, Sueshige Wakisaka, Naruyoshi Fujiwara, Tomoko Suzuki
<p>Transplantation of stem cells which differentiate into more mature neural cells brings about functional improvement in pre-clinical studies of stroke. Previous transplant approaches in diseased brain have utilized injection of the cells in a cell suspension. In addition, neural stem cells were preferentially used as graft. However, these cells had no specific relationship to the damaged tissue of stroke patients and brain injury. The injection of cells in a suspension destroyed the cell-cell interactions that are suggested to be important for promoting functional integrity as cortical motor neurons...
March 17, 2017: Cell Transplantation
https://www.readbyqxmd.com/read/28297671/selective-suppression-of-local-circuits-during-movement-preparation-in-the-mouse-motor-cortex
#13
Masashi Hasegawa, Kei Majima, Takahide Itokazu, Takakuni Maki, Urban-Raphael Albrecht, Nora Castner, Mariko Izumo, Kazuhiro Sohya, Tatsuo K Sato, Yukiyasu Kamitani, Takashi R Sato
Prepared movements are more efficient than those that are not prepared for. Although changes in cortical activity have been observed prior to a forthcoming action, the circuits involved in motor preparation remain unclear. Here, we use in vivo two-photon calcium imaging to uncover changes in the motor cortex during variable waiting periods prior to a forepaw reaching task in mice. Consistent with previous reports, we observed a subset of neurons with increased activity during the waiting period; however, these neurons did not account for the degree of preparation as defined by reaction time (RT)...
March 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/28294153/calretinin-and-neuropeptide-y-interneurons-are-differentially-altered-in-the-motor-cortex-of-the-sod1-g93a-mouse-model-of-als
#14
Rosemary M Clark, Catherine A Blizzard, Kaylene M Young, Anna E King, Tracey C Dickson
Increasing evidence indicates an excitatory/inhibitory imbalance may have a critical role in the pathogenesis of amyotrophic lateral sclerosis (ALS). Impaired inhibitory circuitry is consistently reported in the motor cortex of both familial and sporadic patients, closely associated with cortical hyperexcitability and ALS onset. Inhibitory network dysfunction is presumably mediated by intra-cortical inhibitory interneurons, however, the exact cell types responsible are yet to be identified. In this study we demonstrate dynamic changes in the number of calretinin- (CR) and neuropeptide Y-expressing (NPY) interneurons in the motor cortex of the familial hSOD1(G93A) ALS mouse model, suggesting their potential involvement in motor neuron circuitry defects...
March 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28270750/heterotopic-transcallosal-projections-are-present-throughout-the-mouse-cortex
#15
Alexandra Chovsepian, Laura Empl, Daphne Correa, Florence M Bareyre
Transcallosal projection neurons are a population of pyramidal excitatory neurons located in layers II/III and to a lesser extent layer V of the cortex. Their axons form the corpus callosum thereby providing an inter-hemispheric connection in the brain. While transcallosal projection neurons have been described in some detail before, it is so far unclear whether they are uniformly organized throughout the cortex or whether different functional regions of the cortex contain distinct adaptations of their transcallosal connectivity...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28250409/ontogenetic-establishment-of-order-specific-nuclear-organization-in-the-mammalian-thalamus
#16
Wei Shi, Anjin Xianyu, Zhi Han, Xing Tang, Zhizhong Li, Haining Zhong, Tianyi Mao, Kun Huang, Song-Hai Shi
The thalamus connects the cortex with other brain regions and supports sensory perception, movement, and cognitive function via numerous distinct nuclei. However, the mechanisms underlying the development and organization of diverse thalamic nuclei remain largely unknown. Here we report an intricate ontogenetic logic of mouse thalamic structures. Individual radial glial progenitors in the developing thalamus actively divide and produce a cohort of neuronal progeny that shows striking spatial configuration and nuclear occupation related to functionality...
April 2017: Nature Neuroscience
https://www.readbyqxmd.com/read/28247063/misfolded-sod1-is-not-a-primary-component-of-sporadic-als
#17
Sandrine Da Cruz, Anh Bui, Shahram Saberi, Sandra K Lee, Jennifer Stauffer, Melissa McAlonis-Downes, Derek Schulte, Donald P Pizzo, Philippe A Parone, Don W Cleveland, John Ravits
A common feature of inherited and sporadic ALS is accumulation of abnormal proteinaceous inclusions in motor neurons and glia. SOD1 is the major protein component accumulating in patients with SOD1 mutations, as well as in mutant SOD1 mouse models. ALS-linked mutations of SOD1 have been shown to increase its propensity to misfold and/or aggregate. Antibodies specific for monomeric or misfolded SOD1 have detected misfolded SOD1 accumulating predominantly in spinal cord motor neurons of ALS patients with SOD1 mutations...
February 28, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28237315/loss-of-spatacsin-function-alters-lysosomal-lipid-clearance-leading-to-upper-and-lower-motor-neuron-degeneration
#18
Julien Branchu, Maxime Boutry, Laura Sourd, Marine Depp, Céline Leone, Alexandrine Corriger, Maeva Vallucci, Typhaine Esteves, Raphaël Matusiak, Magali Dumont, Marie-Paule Muriel, Filippo M Santorelli, Alexis Brice, Khalid Hamid El Hachimi, Giovanni Stevanin, Frédéric Darios
Mutations in SPG11 account for the most common form of autosomal recessive hereditary spastic paraplegia (HSP), characterized by a gait disorder associated with various brain alterations. Mutations in the same gene are also responsible for rare forms of Charcot-Marie-Tooth (CMT) disease and progressive juvenile-onset amyotrophic lateral sclerosis (ALS). To elucidate the physiopathological mechanisms underlying these human pathologies, we disrupted the Spg11 gene in mice by inserting stop codons in exon 32, mimicking the most frequent mutations found in patients...
June 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28236105/selection-and-prioritization-of-candidate-drug-targets-for-amyotrophic-lateral-sclerosis-through-a-meta-analysis-approach
#19
Giovanna Morello, Antonio Gianmaria Spampinato, Francesca Luisa Conforti, Velia D'Agata, Sebastiano Cavallaro
Amyotrophic lateral sclerosis (ALS) is a progressive and incurable neurodegenerative disease. Although several compounds have shown promising results in preclinical studies, their translation into clinical trials has failed. This clinical failure is likely due to the inadequacy of the animal models that do not sufficiently reflect the human disease. Therefore, it is important to optimize drug target selection by identifying those that overlap in human and mouse pathology. We have recently characterized the transcriptional profiles of motor cortex samples from sporadic ALS (SALS) patients and differentiated these into two subgroups based on differentially expressed genes, which encode 70 potential therapeutic targets...
April 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28223484/rhythmic-brain-stimulation-reduces-anxiety-related-behavior-in-a-mouse-model-based-on-meditation-training
#20
Aldis P Weible, Denise M Piscopo, Mary K Rothbart, Michael I Posner, Cristopher M Niell
Meditation training induces changes at both the behavioral and neural levels. A month of meditation training can reduce self-reported anxiety and other dimensions of negative affect. It also can change white matter as measured by diffusion tensor imaging and increase resting-state midline frontal theta activity. The current study tests the hypothesis that imposing rhythms in the mouse anterior cingulate cortex (ACC), by using optogenetics to induce oscillations in activity, can produce behavioral changes. Mice were randomly assigned to groups and were given twenty 30-min sessions of light pulses delivered at 1, 8, or 40 Hz over 4 wk or were assigned to a no-laser control condition...
March 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
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