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Leonardo C Faria, Feng Gu, Isabel Parada, Ben Barres, Z David Luo, David A Prince
: The alpha2delta-1 subunit (α2δ-1) of voltage-gated calcium channels is a receptor for astrocyte-secreted thrombospondins that promote developmental synaptogenesis.Alpha2delta-1 receptors are upregulated in models of injury-induced peripheral pain and epileptogenic neocortical trauma associated with an enhancement of excitatory synaptic connectivity. These results lead to the hypothesis that overexpression of α2δ-1 alone in neocortex of uninjured transgenic (TG) mice might result in increased excitatory connectivity and consequent cortical hyperexcitability and epileptiform activity...
February 10, 2017: Neurobiology of Disease
Satomi Moriyama, Masafumi Iharada, Hiroshi Omote, Yoshinori Moriyama, Miki Hiasa
Vesicular glutamate transporter (VGLUT) is an active transporter responsible for vesicular storage of glutamate in synaptic vesicles and plays an essential role in glutamatergic neurotransmission. VGLUT consists of three isoforms, VGLUT1, VGLUT2, and VGLUT3. The VGLUT1 variant, VGLUT1v, with an additional 75-base pair sequence derived from a second intron between exons 2 and 3, which corresponds to 25 amino acid residues in the 1st loop of VGLUT1, is the only splicing variant among VGLUTs, although whether VGLUT1v protein is actually translated at the protein level remains unknown...
February 8, 2017: Biochimica et Biophysica Acta
Kartik Venkatachalam
No abstract text is available yet for this article.
February 1, 2017: Journal of Physiology
Esther Serrano-Saiz, Meital Oren-Suissa, Emily A Bayer, Oliver Hobert
Functional and anatomical sexual dimorphisms in the brain are either the result of cells that are generated only in one sex or a manifestation of sex-specific differentiation of neurons present in both sexes. The PHC neuron pair of the nematode C. elegans differentiates in a strikingly sex-specific manner. In hermaphrodites the PHC neurons display a canonical pattern of synaptic connectivity similar to that of other sensory neurons, but in males PHC differentiates into a densely connected hub sensory neuron/interneuron, integrating a large number of male-specific synaptic inputs and conveying them to both male-specific and sex-shared circuitry...
January 23, 2017: Current Biology: CB
Tetsufumi Ueda
Glutamate is an excitatory neurotransmitter widely used in the vertebrate central nervous systems. The synaptic transmission process is characterized by three steps: (1) presynaptic vesicular transmitter uptake, (2) presynaptic release, and (3) postsynaptic receptor activation. Presynaptic vesicular glutamate uptake plays an initial pivotal role in glutamate transmission by concentrating glutamate in the vesicular lumen prior to its release. This active glutamate transport harnesses energy derived from ATP hydrolysis, and intra- or extravesicular chloride, and is highly specific to glutamate...
2016: Advances in Neurobiology
Masahito Jr Kawamura, David N Ruskin, Susan A Masino
The hippocampus is prone to epileptic seizures and is a key brain region and experimental platform for investigating mechanisms associated with the abnormal neuronal excitability that characterizes a seizure. Accordingly, the hippocampal slice is a common in vitro model to study treatments that may prevent or reduce seizure activity. The ketogenic diet is a metabolic therapy used to treat epilepsy in adults and children for nearly 100 years; it can reduce or eliminate even severe or refractory seizures. New insights into its underlying mechanisms have been revealed by diverse types of electrophysiological recordings in hippocampal slices...
2016: Frontiers in Molecular Neuroscience
Joanna Peris, Kaley MacFadyen, Justin A Smith, Annette D de Kloet, Lei Wang, Eric G Krause
The mesolimbic dopamine (DA) circuitry determines which behaviors are positively reinforcing and therefore should be encoded in the memory to become a part of the behavioral repertoire. Natural reinforcers, like food and sex, activate this pathway, thereby increasing the likelihood of further consummatory, social, and sexual behaviors. Oxytocin (OT) has been implicated in mediating natural reward and OT-synthesizing neurons project to the ventral tegmental area (VTA) and nucleus accumbens (NAc); however, direct neuroanatomical evidence of OT regulation of DA neurons within the VTA is sparse...
September 12, 2016: Journal of Comparative Neurology
Kouji Takeda, Tetsufumi Ueda
Glutamate accumulation into synaptic vesicles is a pivotal step in glutamate transmission. This process is achieved by a vesicular glutamate transporter (VGLUT) coupled to v-type proton ATPase. Normal synaptic transmission, in particular during intensive neuronal firing, would demand rapid transmitter re-filling of emptied synaptic vesicles. We have previously shown that isolated synaptic vesicles are capable of synthesizing glutamate from α-ketoglutarate (not from glutamine) by vesicle-bound aspartate aminotransferase for immediate uptake, in addition to ATP required for uptake by vesicle-bound glycolytic enzymes...
August 26, 2016: Neurochemical Research
Karen P Maruska, Julie M Butler, Karen E Field, Danielle T Porter
Neural communication depends on release and reception of different neurotransmitters within complex circuits that ultimately mediate basic biological functions. We mapped the distribution of glutamatergic, GABAergic, and cholinergic neurons in the brain of the African cichlid fish Astatotilapia burtoni using in situ hybridization to label vesicular glutamate transporters (vglut1, vglut2.1, vglut3), glutamate decarboxylases (gad1, gad2), and choline acetyltransferase (chat). Cells expressing the glutamatergic markers vgluts 1-3 show primarily nonoverlapping distribution patterns, with the most widespread expression observed for vglut2...
February 15, 2017: Journal of Comparative Neurology
Benjamin J Moss, Lidia Park, Caroline L Dahlberg, Peter Juo
Regulation of synaptic AMPA receptor levels is a major mechanism underlying homeostatic synaptic scaling. While in vitro studies have implicated several molecules in synaptic scaling, the in vivo mechanisms linking chronic changes in synaptic activity to alterations in AMPA receptor expression are not well understood. Here we use a genetic approach in C. elegans to dissect a negative feedback pathway coupling levels of the AMPA receptor GLR-1 with its own transcription. GLR-1 trafficking mutants with decreased synaptic receptors in the ventral nerve cord (VNC) exhibit compensatory increases in glr-1 mRNA, which can be attributed to increased glr-1 transcription...
July 2016: PLoS Genetics
M T Hussan, S Saito, Y Atoji
Glutamate acts as the excitatory neurotransmitter in the brain and is mediated largely by the vesicular glutamate transporters (VGLUTs). The objective of the study was to determine the distribution of VGLUT2 mRNA in the turtle brain by in situ hybridization. Intense expression was observed in the olfactory bulb, cerebral cortex, nucleus dorsomedialis thalami, nucleus dorsolateralis thalami, dorsal lateral geniculate nucleus, nucleus reuniens and nucleus periventricularis hypothalami. Moderate expression was noticed in the nucleus rotundus, area lateralis hypothalami, reticular nucleus, cerebellar nucleus and nucleus cochlearis...
July 11, 2016: Anatomia, Histologia, Embryologia
Hong-Sheng Wang, Gang Yu, Zhi-Tong Wang, Shou-Pu Yi, Rui-Bin Su, Ze-Hui Gong
Disturbance of glutamate homeostasis is a well-characterized mechanism of neuropathic pain. Vesicular glutamate transporters (VGLUTs) determine glutamate accumulation in synaptic vesicles and their roles in neuropathic pain have been suggested by gene-knockout studies. Here, we investigated the spatio-temporal changes in VGLUT expression during the development of neuropathic pain in wild-type rats. Spared nerve injury (SNI) induced mechanical allodynia from postoperative day 1 to at least day 14. Expression of VGLUT1 and VGLUT2 in dorsal root ganglia and spinal cord was examined by western blot analyses on different postoperative days...
October 2016: Neurochemistry International
Rebecca P Seal
The somatosensory system transmits touch, temperature, itch and pain. Three vesicular glutamate transporter isoforms mediate the release of glutamate throughout the mammalian nervous system with largely non-overlapping distributions and unique roles at the synapse. This review discusses the contribution of each of these essential transporters to circuits underlying pain and other somatosensory behaviors throughout postnatal development and in the adult. A better understanding of the individual contributions of the VGLUT isoforms could provide new avenues for therapeutic intervention...
September 2016: Neurochemistry International
Jacob Eriksen, Roger Chang, Matt McGregor, Katlin Silm, Toshiharu Suzuki, Robert H Edwards
The quantal nature of synaptic transmission requires a mechanism to transport neurotransmitter into synaptic vesicles without promoting non-vesicular efflux across the plasma membrane. Indeed, the vesicular transport of most classical transmitters involves a mechanism of H(+) exchange, which restricts flux to acidic membranes such as synaptic vesicles. However, vesicular transport of the principal excitatory transmitter glutamate depends primarily on membrane potential, which would drive non-vesicular efflux, and the role of protons is unclear...
May 18, 2016: Neuron
Yanjing Cao, Zengmei Gou, Yifeng Du, Yongjun Fan, Lizhen Liang, Yongxing Yan, Ping Lin, Mudan Jin, Yifenf Du
Chronic cerebral ischemia (CCI) is associated with cognitive decline in aging, vascular dementia and Alzheimer's disease. Substantial evidence has shown that chronic cerebral ischemia may cause cognitive impairment, but the underlying neurobiological mechanism is poorly understood so far. In the present study, we used a rat model of chronic cerebral ischemia by permanent bilateral common carotid artery occlusion (BCCAO) to investigate the alterations of glutamatergic and central cholinergic dysfunction, and their causal relationship with the cognitive deficits induced by chronic cerebral ischemia...
May 4, 2016: Neuroscience Letters
Youichi Uda, Shuai Xu, Takafumi Matsumura, Yoshinori Takei
Neural stem cells (NSCs) produce all neuronal subtypes involved in the nervous system. The mechanism regulating their subtype selection is not fully understood. We found that the expression of the nucleotide receptor P2Y4 was transiently augmented in the course of neuronal differentiation of mouse embryonic stem cells (ESCs), which was after loss of pluripotency but prior to terminal differentiation of neurons. The activation of P2Y4 in the differentiating ESCs resulted in an increased proportion of neurons expressing vesicular glutamate transporter (vGluT), a marker of glutamatergic subtype...
April 12, 2016: Stem Cell Reports
Fei Yu, Shuai Hao, Bo Yang, Yue Zhao, Wenyue Zhang, Jun Yang
Mild maternal iron deficiency anemia (IDA) adversely affects the development of cochlear hair cells of the young offspring, but the mechanisms underlying the association are incompletely understood. The aim of this study was to evaluate whether mild maternal IDA in guinea pigs could interrupt inner hair cell (IHC) ribbon synapse density and outer hair cell motility of the offspring. Here, we established a dietary restriction model that allows us to study quantitative changes in the number of IHC ribbon synapses and hearing impairment in response to mild maternal IDA in young guinea pig...
May 2016: Neurotoxicity Research
Agnieszka Münster-Wandowski, Johannes-Friedrich Zander, Karin Richter, Gudrun Ahnert-Hilger
The vesicular transmitter transporters VGLUT, VGAT, VMAT2 and VAChT, define phenotype and physiological properties of neuronal subtypes. VGLUTs concentrate the excitatory amino acid glutamate, VGAT the inhibitory amino acid GABA, VMAT2 monoamines, and VAChT acetylcholine (ACh) into synaptic vesicle (SV). Following membrane depolarization SV release their content into the synaptic cleft. A strict segregation of vesicular transporters is mandatory for the precise functioning of synaptic communication and of neuronal circuits...
2016: Frontiers in Synaptic Neuroscience
Tetsufumi Ito, Yasuro Atoji
Inhibitory feedforward projection is one of key features of the organization of the central auditory system. In mammals, the inferior colliculus (IC) is the origin of a substantial inhibitory feedforward projection as well as an excitatory projection to the auditory thalamus. This inhibitory feedforward projection is provided by large γ-aminobutyric acid (GABA)ergic (LG) neurons, which are characterized by their receipt of dense excitatory axosomatic terminals positive for vesicular glutamate transporter (VGLUT) 2...
September 1, 2016: Journal of Comparative Neurology
Callista B Harper, Andreas Papadopulos, Sally Martin, Daniel R Matthews, Garry P Morgan, Tam H Nguyen, Tong Wang, Deepak Nair, Daniel Choquet, Frederic A Meunier
Neuronal communication relies on synaptic vesicles undergoing regulated exocytosis and recycling for multiple rounds of fusion. Whether all synaptic vesicles have identical protein content has been challenged, suggesting that their recycling ability may differ greatly. Botulinum neurotoxin type-A (BoNT/A) is a highly potent neurotoxin that is internalized in synaptic vesicles at motor nerve terminals and induces flaccid paralysis. Recently, BoNT/A was also shown to undergo retrograde transport, suggesting it might enter a specific pool of synaptic vesicles with a retrograde trafficking fate...
January 25, 2016: Scientific Reports
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