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https://www.readbyqxmd.com/read/27926833/conformational-plasticity-in-the-transsynaptic-neurexin-cerebellin-glutamate-receptor-adhesion-complex
#1
Shouqiang Cheng, Alpay B Seven, Jing Wang, Georgios Skiniotis, Engin Özkan
Synaptic specificity is a defining property of neural networks. In the cerebellum, synapses between parallel fiber neurons and Purkinje cells are specified by the simultaneous interactions of secreted protein cerebellin with pre-synaptic neurexin and post-synaptic delta-type glutamate receptors (GluD). Here, we determined the crystal structures of the trimeric C1q-like domain of rat cerebellin-1, and the first complete ectodomain of a GluD, rat GluD2. Cerebellin binds to the LNS6 domain of α- and β-neurexin-1 through a high-affinity interaction that involves its highly flexible N-terminal domain...
December 6, 2016: Structure
https://www.readbyqxmd.com/read/27926574/neural-activity-memory-and-dementias-serotonergic-markers
#2
Alfredo Meneses
Dysfunctional memory seems to be a key component of diverse dementias and other neuropsychiatric disorders; unfortunately, no effective treatment exists for this, probably because of the absence of neural biomarkers accompanying it. Diverse neurotransmission systems have been implicated in memory, including serotonin or 5-hydroxytryptamine (5-HT). There are multiple serotonergic pharmacological tools, well-characterized downstream signaling in mammals' species and neural markers providing new insights into memory functions and dysfunctions...
December 6, 2016: Behavioural Pharmacology
https://www.readbyqxmd.com/read/27923234/transient-receptor-potential-vanilloid-1-channels-contribute-to-the-regulation-of-acid-and-base-induced-vasomotor-responses
#3
Ivan Ivic, Margit Solymar, Eszter Pakai, Zoltan Rumbus, Erika Pinter, Akos Koller, Andras Garami
pH changes can influence local blood flow, but the mechanisms of how acids and bases affect vascular tone is not fully clarified. Transient receptor potential vanilloid-1 (TRPV1) channels are expressed in vessels and can be activated by pH alterations. Thus, we hypothesized that TRPV1 channels are involved in the mediation of vascular responses to acid-base changes. Vasomotor responses to HCl, NaOH, and capsaicin were measured in isolated murine carotid and tail skin arteries. The function of TRPV1 was blocked by either of three approaches: Trpv1 gene disruption, pharmacological blockade with a TRPV1 antagonist (BCTC), and functional impairment of mainly neural TRPV1 channels (desensitization)...
December 7, 2016: Journal of Vascular Research
https://www.readbyqxmd.com/read/27922061/thermo-sensitive-hydrogels-combined-with-decellularised-matrix-deliver-bfgf-for-the-functional-recovery-of-rats-after-a-spinal-cord-injury
#4
He-Lin Xu, Fu-Rong Tian, Cui-Tao Lu, Jie Xu, Zi-Liang Fan, Jing-Jing Yang, Pian-Pian Chen, Ya-Dong Huang, Jian Xiao, Ying-Zheng Zhao
Because of the short half-life, either systemic or local administration of bFGF shows significant drawbacks to spinal injury. In this study, an acellular spinal cord scaffold (ASC) was encapsulated in a thermo-sensitive hydrogel to overcome these limitations. The ASC was firstly prepared from the spinal cord of healthy rats and characterized by scanning electronic microscopy and immunohistochemical staining. bFGF could specifically complex with the ASC scaffold via electrostatic or receptor-mediated interactions...
December 6, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27919795/current-and-novel-insights-into-the-neurophysiology-of-migraine-and-its-implications-for-therapeutics
#5
REVIEW
Simon Akerman, Marcela Romero-Reyes, Philip R Holland
Migraine headache and its associated symptoms have plagued humans for two millennia. It is manifest throughout the world, and affects more than 1/6 of the global population. It is the most common brain disorder, and is characterized by moderate to severe unilateral headache that is accompanied by vomiting, nausea, photophobia, phonophobia, and other hypersensitive symptoms of the senses. While there is still a clear lack of understanding of its neurophysiology, it is beginning to be understood, and it seems to suggest migraine is a disorder of brain sensory processing, characterized by a generalized neuronal hyperexcitability...
December 2, 2016: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/27918530/a-probabilistic-approach-to-demixing-odors
#6
Agnieszka Grabska-Barwińska, Simon Barthelmé, Jeff Beck, Zachary F Mainen, Alexandre Pouget, Peter E Latham
The olfactory system faces a hard problem: on the basis of noisy information from olfactory receptor neurons (the neurons that transduce chemicals to neural activity), it must figure out which odors are present in the world. Odors almost never occur in isolation, and different odors excite overlapping populations of olfactory receptor neurons, so the central challenge of the olfactory system is to demix its input. Because of noise and the large number of possible odors, demixing is fundamentally a probabilistic inference task...
December 5, 2016: Nature Neuroscience
https://www.readbyqxmd.com/read/27918106/cannabidiol-activates-neuronal-precursor-genes-in-human-gingival-mesenchymal-stromal-cells
#7
Thangavelu Soundara Rajan, Sabrina Giacoppo, Domenico Scionti, Francesca Diomede, Gianpaolo Grassi, Federica Pollastro, Adriano Piattelli, Placido Bramanti, Emanuela Mazzon, Oriana Trubiani
In the last years, mesenchymal stromal cells (MSCs) from oral tissues have received considerable interest in regenerative medicine since they can be obtained with minimal invasive procedure and exhibit immunomodulatory properties. This study was aimed to investigate whether in vitro pre-treatment of MSCs obtained from human gingiva (hGMSCs) with Cannabidiol (CBD), a cannabinoid component produced by the plant Cannabis sativa, may promote human gingiva derived MSCs to differentiate towards neuronal precursor cells...
December 5, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27917940/ubiquitin-ligase-nedd4-regulates-ppar%C3%AE-stability-and-adipocyte-differentiation-in-3t3-l1-cells
#8
Jing Jing Li, Ruishan Wang, Rati Lama, Xinjiang Wang, Z Elizabeth Floyd, Edwards A Park, Francesca-Fang Liao
Peroxisome proliferator-activated receptor-γ (PPARγ) is a ligand-activated nuclear receptor which controls lipid and glucose metabolism. It is also the master regulator of adipogenesis. In adipocytes, ligand-dependent PPARγ activation is associated with proteasomal degradation; therefore, regulation of PPARγ degradation may modulate its transcriptional activity. Here, we show that neural precursor cell expressed developmentally down-regulated protein 4 (NEDD4), an E3 ubiquitin ligase, interacts with the hinge and ligand binding domains of PPARγ and is a bona fide E3 ligase for PPARγ...
December 5, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27916472/generation-of-neural-cells-using-ipscs-from-sleep-bruxism-patients-with-5-ht2a-polymorphism
#9
Yurie Hoashi, Satoshi Okamoto, Yuka Abe, Takashi Matsumoto, Junichi Tanaka, Yuya Yoshida, Kent Imaizumi, Kenji Mishima, Wado Akamatsu, Hideyuki Okano, Kazuyoshi Baba
PURPOSE: Sleep bruxism (SB) is classified as a sleep-related movement disorder characterized by grinding and clenching of the teeth during sleep, which is responsible for a variety of clinical problems such as abnormal tooth attrition and fracture of teeth or roots. Little is known about the etiology of SB. Our previous study identified a genomic association of the serotonin 2A receptor (5-HT2A) single nucleotide polymorphism (SNP), rs6313 C>T, with SB, where the C allele carrier is associated with a 4...
December 1, 2016: Journal of Prosthodontic Research
https://www.readbyqxmd.com/read/27916456/acute-fasting-regulates-retrograde-synaptic-enhancement-through-a-4e-bp-dependent-mechanism
#10
Grant Kauwe, Kazuya Tsurudome, Jay Penney, Megumi Mori, Lindsay Gray, Mario R Calderon, Fatima Elazouzzi, Nicole Chicoine, Nahum Sonenberg, A Pejmun Haghighi
While beneficial effects of fasting on organismal function and health are well appreciated, we know little about the molecular details of how fasting influences synaptic function and plasticity. Our genetic and electrophysiological experiments demonstrate that acute fasting blocks retrograde synaptic enhancement that is normally triggered as a result of reduction in postsynaptic receptor function at the Drosophila larval neuromuscular junction (NMJ). This negative regulation critically depends on transcriptional enhancement of eukaryotic initiation factor 4E binding protein (4E-BP) under the control of the transcription factor Forkhead box O (Foxo)...
November 21, 2016: Neuron
https://www.readbyqxmd.com/read/27915167/examining-fkbp5-mrna-expression-in-human-ipsc-derived-neural-cells
#11
Richard Lieberman, Henry R Kranzler, Eric S Levine, Jonathan Covault
In peripheral blood leukocytes, FKBP5 mRNA expression is upregulated following glucocorticoid receptor activation. The single nucleotide polymorphism rs1360780 in FKBP5 is associated with psychiatric illness and has functional molecular effects. However, examination of FKBP5 regulation has largely been limited to peripheral cells, which may not reflect regulation in neural cells. We used 27 human induced pluripotent stem cell lines (iPSCs) derived from 20 subjects to examine FKBP5 mRNA expression following GR activation...
November 24, 2016: Psychiatry Research
https://www.readbyqxmd.com/read/27913633/chemorepellent-semaphorin-3e-negatively-regulates-neutrophil-migration-in-vitro-and-in-vivo
#12
Hesam Movassagh, Abeer Saati, Saravanan Nandagopal, Ashfaque Mohammed, Nazanin Tatari, Lianyu Shan, Jonathan S Duke-Cohan, Keith R Fowke, Francis Lin, Abdelilah S Gounni
Neutrophil migration is an essential step in leukocyte trafficking during inflammatory responses. Semaphorins, originally discovered as axon guidance cues in neural development, have been shown to regulate cell migration beyond the nervous system. However, the potential contribution of semaphorins in the regulation of neutrophil migration is not well understood. This study examines the possible role of a secreted chemorepellent, Semaphorin 3E (Sema3E), in neutrophil migration. In this study, we demonstrated that human neutrophils constitutively express Sema3E high-affinity receptor, PlexinD1...
December 2, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27913423/bronchodilatory-effect-of-deep-inspiration-in-freshly-isolated-sheep-lungs
#13
William D Wong, Lu Wang, Peter D Paré, Chun Y Seow
Taking a big breath is known to reverse bronchoconstriction induced by bronchochallenge in healthy subjects; this bronchodilatory effect of deep inspiration (DI) is diminished in asthmatics. The mechanism underlying the DI effect is not clear. Observations from experiments using isolated airway smooth muscle (ASM) preparations and airway segments suggest that straining of ASM due to DI could lead to bronchodilation, possibly due to strain-induced reduction in ASM contractility. However, factors external to the lung cannot be excluded as potential causes for the DI effect...
December 2, 2016: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://www.readbyqxmd.com/read/27913408/neurophysiological-mechanisms-of-cortical-plasticity-impairments-in-schizophrenia-and-modulation-by-the-nmda-receptor-agonist-d-serine
#14
Joshua T Kantrowitz, Michael L Epstein, Odeta Beggel, Stephanie Rohrig, Jonathan M Lehrfeld, Nadine Revheim, Nayla P Lehrfeld, Jacob Reep, Emily Parker, Gail Silipo, Merav Ahissar, Daniel C Javitt
Schizophrenia is associated with deficits in cortical plasticity that affect sensory brain regions and lead to impaired cognitive performance. Here we examined underlying neural mechanisms of auditory plasticity deficits using combined behavioural and neurophysiological assessment, along with neuropharmacological manipulation targeted at the N-methyl-D-aspartate type glutamate receptor (NMDAR). Cortical plasticity was assessed in a cohort of 40 schizophrenia/schizoaffective patients relative to 42 healthy control subjects using a fixed reference tone auditory plasticity task...
December 2016: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/27911847/zika-virus-cell-tropism-in-the-developing-human-brain-and-inhibition-by-azithromycin
#15
Hanna Retallack, Elizabeth Di Lullo, Carolina Arias, Kristeene A Knopp, Matthew T Laurie, Carmen Sandoval-Espinosa, Walter R Mancia Leon, Robert Krencik, Erik M Ullian, Julien Spatazza, Alex A Pollen, Caleigh Mandel-Brehm, Tomasz J Nowakowski, Arnold R Kriegstein, Joseph L DeRisi
The rapid spread of Zika virus (ZIKV) and its association with abnormal brain development constitute a global health emergency. Congenital ZIKV infection produces a range of mild to severe pathologies, including microcephaly. To understand the pathophysiology of ZIKV infection, we used models of the developing brain that faithfully recapitulate the tissue architecture in early to midgestation. We identify the brain cell populations that are most susceptible to ZIKV infection in primary human tissue, provide evidence for a mechanism of viral entry, and show that a commonly used antibiotic protects cultured brain cells by reducing viral proliferation...
November 29, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27911758/multimodal-imaging-for-dreadd-expressing-neurons-in-living-brain-and-their-application-to-implantation-of-ipsc-derived-neural-progenitors
#16
Bin Ji, Hiroyuki Kaneko, Takafumi Minamimoto, Haruhisa Inoue, Hiroki Takeuchi, Katsushi Kumata, Ming-Rong Zhang, Ichio Aoki, Chie Seki, Maiko Ono, Masaki Tokunaga, Satoshi Tsukamoto, Koji Tanabe, Ryong-Moon Shin, Takeharu Minamihisamatsu, Seiji Kito, Barry J Richmond, Tetsuya Suhara, Makoto Higuchi
: Chemogenetic manipulation of neuronal activities has been enabled by a designer receptor (designer receptor exclusively activated by designer drugs, DREADD) that is activated exclusively by clozapine-N-oxide (CNO). Here, we applied CNO as a functional reporter probe to positron emission tomography (PET) of DREADD in living brains. Mutant human M4 DREADD (hM4Di) expressed in transgenic (Tg) mouse neurons was visualized by PET with microdose [(11)C]CNO. Deactivation of DREADD-expressing neurons in these mice by nonradioactive CNO at a pharmacological dose could also be captured by arterial spin labeling MRI (ASL-MRI)...
November 9, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27910896/methylmercury-induces-the-expression-of-tnf-%C3%AE-selectively-in-the-brain-of-mice
#17
Miyuki Iwai-Shimada, Tsutomu Takahashi, Min-Seok Kim, Masatake Fujimura, Hitoyasu Ito, Takashi Toyama, Akira Naganuma, Gi-Wook Hwang
Methylmercury selectively damages the central nervous system (CNS). The tumor necrosis factor (TNF) superfamily includes representative cytokines that participate in the inflammatory response as well as cell survival, and apoptosis. In this study, we found that administration of methylmercury selectively induced TNF-α expression in the brain of mice. Although the accumulated mercury concentration in the liver and kidneys was greater than in the brain, TNF-α expression was induced to a greater extent in brain...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27909152/involvement-of-mesolimbic-dopaminergic-network-in-neuropathic-pain-relief-by-treadmill-exercise-a-study-for-specific-neural-control-with-gi-dreadd-in-mice
#18
Kenta Wakaizumi, Takashige Kondo, Yusuke Hamada, Michiko Narita, Rui Kawabe, Hiroki Narita, Moe Watanabe, Shigeki Kato, Emiko Senba, Kazuto Kobayashi, Naoko Kuzumaki, Akihiro Yamanaka, Hiroshi Morisaki, Minoru Narita
BACKGROUND: Exercise alleviates pain and it is a central component of treatment strategy for chronic pain in clinical setting. However, little is known about mechanism of this exercise-induced hypoalgesia. The mesolimbic dopaminergic network plays a role in positive emotions to rewards including motivation and pleasure. Pain negatively modulates these emotions, but appropriate exercise is considered to activate the dopaminergic network. We investigated possible involvement of this network as a mechanism of exercise-induced hypoalgesia...
2016: Molecular Pain
https://www.readbyqxmd.com/read/27909096/excitatory-hindbrain-forebrain-communication-is-required-for-cisplatin-induced-anorexia-and-weight-loss
#19
Amber L Alhadeff, Ruby A Holland, Huiyuan Zheng, Linda Rinaman, Harvey J Grill, Bart C De Jonghe
: Cisplatin chemotherapy is commonly used to treat cancer despite severe energy balance side effects. In rats, cisplatin activates nucleus tractus solitarius (NTS) projections to the lateral parabrachial nucleus (lPBN), and calcitonin-gene related peptide (CGRP) projections from the lPBN to the central nucleus of the amygdala (CeA). We previously demonstrated that CeA glutamate receptor signaling mediates cisplatin-induced anorexia and body weight loss. Here, we use neuroanatomical tracing, immunofluorescence and confocal imaging to demonstrate that virtually all NTS→lPBN and lPBN→CeA CGRP projections co-express vesicular glutamate transporter 2 (VGLUT2), providing evidence that excitatory projections mediate cisplatin-induced energy balance dysregulation...
December 1, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27908934/gata6-promotes-hair-follicle-progenitor-cell-renewal-by-genome-maintenance-during-proliferation
#20
Alex B Wang, Ying V Zhang, Tudorita Tumbar
Cell proliferation is essential to rapid tissue growth and repair, but can result in replication-associated genome damage. Here, we implicate the transcription factor Gata6 in adult mouse hair follicle regeneration where it controls the renewal of rapidly proliferating epithelial (matrix) progenitors and hence the extent of production of terminally differentiated lineages. We find that Gata6 protects against DNA damage associated with proliferation, thus preventing cell cycle arrest and apoptosis. Furthermore, we show that in vivo Gata6 stimulates EDA-receptor signaling adaptor Edaradd level and NF-κB pathway activation, known to be important for DNA damage repair and stress response in general and for hair follicle growth in particular...
December 1, 2016: EMBO Journal
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