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https://www.readbyqxmd.com/read/28102468/mutation-of-the-herc-1-ubiquitin-ligase-impairs-associative-learning-in-the-lateral-amygdala
#1
Eva Mª Pérez-Villegas, José V Negrete-Díaz, Mª Elena Porras-García, Rocío Ruiz, Angel M Carrión, Antonio Rodríguez-Moreno, José A Armengol
Tambaleante (tbl/tbl) is a mutant mouse that carries a spontaneous Gly483Glu substitution in the HERC1 (HECT domain and RCC1 domain) E3 ubiquitin ligase protein (HERC1). The tbl/tbl mutant suffers an ataxic syndrome given the almost complete loss of cerebellar Purkinje cells during adult life. More recent analyses have identified alterations at neuromuscular junctions in these mice, as well as in other neurons of the central nervous system, such as motor neurons in the spinal cord, or pyramidal neurons in the hippocampal CA3 region and the neocortex...
January 19, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28100750/target-dependent-compartmentalization-of-the-corelease-of-glutamate-and-gaba-from-the-mossy-fibers
#2
Emilio J Galván, Rafael Gutiérrez
: The mossy fibers (MFs) corelease glutamate and GABA onto pyramidal cells of CA3 during development, until the end of the third postnatal week. However, the major target cells of the MF are the interneurons of CA3. Therefore, it has been shown that the interneurons of the hilus and stratum lucidum receive this dual monosynaptic input on MF stimulation. Because the plasticity of glutamatergic transmission from the different terminals of the MF is target specific, we here asked whether the corelease of glutamate and GABA was also subjected to a target-dependent compartmentalization...
January 18, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28100738/mir-142-3p-is-a-key-regulator-of-il-1%C3%AE-dependent-synaptopathy-in-neuroinflammation
#3
Georgia Mandolesi, Francesca De Vito, Alessandra Musella, Antonietta Gentile, Silvia Bullitta, Diego Fresegna, Helena Sepman, Claudio Di Sanza, Nabila Haji, Francesco Mori, Fabio Buttari, Emerald Perlas, Maria Teresa Ciotti, Eran Hornstein, Irene Bozzoni, Carlo Presutti, Diego Centonze
: MicroRNAs (miRNA) play an important role in post-transcriptional gene regulation of several physiological and pathological processes. In multiple sclerosis (MS), a chronic inflammatory and degenerative disease of the CNS, and in its mouse model, the experimental autoimmune encephalomyelitis (EAE), miRNA dysregulation has been mainly related to immune system dysfunction and white matter (WM) pathology. However, little is known about their role in gray matter pathology. Here, we explored miRNA involvement in the inflammation-driven alterations of synaptic structure and function, collectively known as synaptopathy, a neuropathological process contributing to excitotoxic neurodegeneration in MS/EAE...
January 18, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28100490/amino-terminal-domains-of-kainate-receptors-determine-the-differential-dependence-on-neto-auxiliary-subunits-for-trafficking
#4
Nengyin Sheng, Yun Stone Shi, Roger A Nicoll
The kainate receptor (KAR), a subtype of glutamate receptor, mediates excitatory synaptic responses at a subset of glutamatergic synapses. However, the molecular mechanisms underlying the trafficking of its different subunits are poorly understood. Here we use the CA1 hippocampal pyramidal cell, which lacks KAR-mediated synaptic currents, as a null background to determine the minimal requirements for the extrasynaptic and synaptic expression of the GluK2 subunit. We find that the GluK2 receptor itself, in contrast to GluK1, traffics to the neuronal surface and synapse efficiently and the auxiliary subunits Neto1 and Neto2 caused no further enhancement of these two trafficking processes...
January 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28098946/negative-association-between-mr-spectroscopic-glutamate-markers-and-gray-matter-volume-after-alcohol-withdrawal-in-the-hippocampus-a-translational-study-in-humans-and-rats
#5
Ulrich Frischknecht, Derik Hermann, Nuran Tunc-Skarka, Guo-Ying Wang, Markus Sack, Julia van Eijk, Traute Demirakca, Claudia Falfan-Melgoza, Bertram Krumm, Sandra Dieter, Rainer Spanagel, Falk Kiefer, Karl F Mann, Wolfgang H Sommer, Gabriele Ende, Wolfgang Weber-Fahr
BACKGROUND: Both chronic alcohol consumption and alcohol withdrawal lead to neural tissue damage which partly recovers during abstinence. This study investigated withdrawal-associated changes in glutamatergic compounds, markers of neuronal integrity, and gray matter volumes during acute alcohol withdrawal in the hippocampus, a key region in development and maintenance of alcohol dependence in humans and rats. METHODS: Alcohol-dependent patients (N = 39) underwent magnetic resonance imaging (MRI) and MR spectroscopy (MRS) measurements within 24 hours after the last drink and after 2 weeks of abstinence...
January 18, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28097486/the-therapeutic-effectiveness-of-delayed-fetal-spinal-cord-tissue-transplantation-on-respiratory-function-following-mid-cervical-spinal-cord-injury
#6
Chia-Ching Lin, Sih-Rong Lai, Yu-Han Shao, Chun-Lin Chen, Kun-Ze Lee
Respiratory impairment due to damage of the spinal respiratory motoneurons and interruption of the descending drives from brainstem premotor neurons to spinal respiratory motoneurons is the leading cause of morbidity and mortality following cervical spinal cord injury. The present study was designed to evaluate the therapeutic effectiveness of delayed transplantation of fetal spinal cord (FSC) tissue on respiratory function in rats with mid-cervical spinal cord injury. Embryonic day-14 rat FSC tissue was transplanted into a C4 spinal cord hemilesion cavity in adult male rats at 1 week postinjury...
January 17, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28097463/neurokinin-1-receptor-immunopositive-neurons-in-the-medullary-dorsal-horn-provide-collateral-axons-to-both-the-thalamus-and-parabrachial-nucleus-in-rats
#7
Xu Li, Shun-Nan Ge, Yang Li, Han-Tao Wang
It has been suggested that the trigemino-thalamic and trigemino-parabrachial projection neurons in the medullary dorsal horn (MDH) are highly implicated in the sensory-discriminative and emotional/affective aspects of orofacial pain, respectively. In previous studies, some neurons were reported to send projections to both the thalamus and parabrachial nucleus by way of collaterals in the MDH. However, little is known about the chemoarchitecture of this group of neurons. Thus, in the present study, we determined whether the neurokinin-1 (NK-1) receptor, which is crucial for primary orofacial pain signaling, was expressed in MDH neurons co-innervating the thalamus and parabrachial nucleus...
January 17, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28097219/key-role-of-the-dopamine-d4-receptor-in-the-modulation-of-corticostriatal-glutamatergic-neurotransmission
#8
Jordi Bonaventura, César Quiroz, Ning-Sheng Cai, Marcelo Rubinstein, Gianluigi Tanda, Sergi Ferré
Polymorphic variants of the dopamine D4 receptor gene (DRD4) have been repeatedly associated with numerous neuropsychiatric disorders. Yet, the functional role of the D4 receptor and the functional differences of the products of DRD4 polymorphic variants remained enigmatic. Immunohistochemical and optogenetic-microdialysis experiments were performed in knock-in mice expressing a D4 receptor with the long intracellular domain of a human DRD4 polymorphic variant associated with attention deficit hyperactivity disorder (ADHD)...
January 2017: Science Advances
https://www.readbyqxmd.com/read/28096412/transmembrane-protein-108-is-required-for-glutamatergic-transmission-in-dentate-gyrus
#9
Hui-Feng Jiao, Xiang-Dong Sun, Ryan Bates, Lei Xiong, Lei Zhang, Fang Liu, Lei Li, Hong-Sheng Zhang, Shun-Qi Wang, Ming-Tao Xiong, Mihir Patel, Alexis M Stranahan, Wen-Cheng Xiong, Bao-Ming Li, Lin Mei
Neurotransmission in dentate gyrus (DG) is critical for spatial coding, learning memory, and emotion processing. Although DG dysfunction is implicated in psychiatric disorders, including schizophrenia, underlying pathological mechanisms remain unclear. Here we report that transmembrane protein 108 (Tmem108), a novel schizophrenia susceptibility gene, is highly enriched in DG granule neurons and its expression increased at the postnatal period critical for DG development. Tmem108 is specifically expressed in the nervous system and enriched in the postsynaptic density fraction...
January 17, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28093558/glutamatergic-synapses-are-structurally-and-biochemically-complex-because-of-multiple-plasticity-processes-long-term-potentiation-long-term-depression-short-term-potentiation-and-scaling
#10
REVIEW
John Lisman
Synapses are complex because they perform multiple functions, including at least six mechanistically different forms of plasticity. Here, I comment on recent developments regarding these processes. (i) Short-term potentiation (STP), a Hebbian process that requires small amounts of synaptic input, appears to make strong contributions to some forms of working memory. (ii) The rules for long-term potentiation (LTP) induction in CA3 have been clarified: induction does not depend obligatorily on backpropagating sodium spikes but, rather, on dendritic branch-specific N-methyl-d-aspartate (NMDA) spikes...
March 5, 2017: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/28093336/peripheral-nerve-injury-potentiates-excitatory-synaptic-transmission-in-locus-coeruleus-neurons
#11
Kambiz Rohampour, Hossein Azizi, Yaghoub Fathollahi, Saeed Semnanian
Peripheral nerve injury (PNI) is believed to cause maladaptive changes at synaptic level, leading to neuropathic pain which is difficult to treat with common analgesic drugs. Noradrenergic locus coeruleus (LC) neurons have a crucial role in neuropathic pain modulation. In this study we examined whether chronic constriction injury (CCI) could affect glutamatergic synaptic transmission in LC neurons. CCI was performed on P10 to P12 Sprague Dawley pups. Seven days after CCI, horizontal slices of brainstem (300μm thick) were prepared and whole-cell patch clamp recording was performed...
January 13, 2017: Brain Research Bulletin
https://www.readbyqxmd.com/read/28092469/investigational-drugs-in-recent-clinical-trials-for-treatment-resistant-depression
#12
Ricardo P Garay, Carlos A Zarate, Thomas Charpeaud, Leslie Citrome, Christoph U Correll, Ahcène Hameg, Pierre-Michel Llorca
The authors describe the medications for treatment-resistant depression (TRD) in phase II/III of clinical development in the EU and US and provide an opinion on how current treatment can be improved in the near future. Areas covered: Sixty-two trials were identified in US and EU clinical trial registries that included six investigational compounds in recent phase III development and 12 others in recent phase II clinical trials. Glutamatergic agents have been the focus of many studies. A single intravenous dose of the glutamatergic modulator ketamine produces a robust and rapid antidepressant effect in persons with TRD; this effect continues to remain significant for 1 week...
January 16, 2017: Expert Review of Neurotherapeutics
https://www.readbyqxmd.com/read/28089695/the-pharmacology-of-tacrine-at-n-methyl-d-aspartate-receptors
#13
REVIEW
Martin Horak, Kristina Holubova, Eugenie Nepovimova, Jan Krusek, Martina Kaniakova, Jan Korabecny, Ladislav Vyklicky, Kamil Kuca, Ales Stuchlik, Jan Ricny, Karel Vales, Ondrej Soukup
The mechanism of tacrine as a precognitive drug has been considered to be complex and not fully understood. It has been reported to involve a wide spectrum of targets involving cholinergic, gabaergic, nitrinergic and glutamatergic pathways. Here, we review the effect of tacrine and its derivatives on the NMDA receptors (NMDAR) with a focus on the mechanism of action and biological consequences related to the Alzheimer's disease treatment. Our findings indicate that effect of tacrine on glutamatergic neurons is both direct and indirect...
January 13, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28086761/is-treatment-resistant-schizophrenia-categorically-distinct-from-treatment-responsive-schizophrenia-a-systematic-review
#14
Amy L Gillespie, Ruta Samanaite, Jonathan Mill, Alice Egerton, James H MacCabe
BACKGROUND: Schizophrenia is a highly heterogeneous disorder, and around a third of patients are treatment-resistant. The only evidence-based treatment for these patients is clozapine, an atypical antipsychotic with relatively weak dopamine antagonism. It is plausible that varying degrees of response to antipsychotics reflect categorically distinct illness subtypes, which would have significant implications for research and clinical practice. If these subtypes could be distinguished at illness onset, this could represent a first step towards personalised medicine in psychiatry...
January 13, 2017: BMC Psychiatry
https://www.readbyqxmd.com/read/28079059/co-variation-of-peripheral-levels-of-mir-1202-and-brain-activity-and-connectivity-during-antidepressant-treatment
#15
Juan Pablo Lopez, Fabricio Pereira, Stéphane Richard-Devantoy, Marcelo Berlim, Eduardo Chachamovich, Laura M Fiori, Paola Niola, Gustavo Turecki, Fabrice Jollant
MicroRNAs are short non-coding molecules that play a major role in regulating gene expression. Peripheral levels of miR-1202 have been shown to predict and mediate antidepressant response. However, it is not clear to what extent these peripheral measures reflect central neural changes in vivo. We approached this problem with the combined use of peripheral miR-1202 measures and neuroimaging. At baseline and after 8 weeks of Desvenlafaxine (50-100 mg die), twenty patients were scanned with 3T Magnetic Resonance Imaging, first at rest then during the Go/NoGo task, a classical test of response inhibition...
January 12, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28074534/depolarizing-gaba-contributes-to-glutamatergic-network-rewiring-in-epilepsy
#16
Nazim Kourdougli, Christophe Pellegrino, Juho-Matti Renko, Stanislav Khirug, Geneviève Chazal, Tiina-Kaisa Kukko-Lukjanov, Sari E Lauri, Jean-Luc Gaiarsa, Liang Zhou, Angélique Peret, Eero Castrén, Raimo Kalevi Tuominen, Valérie Crépel, Claudio Rivera
OBJECTIVE: Rewiring of excitatory glutamatergic neuronal circuits is a major abnormality in epilepsy. Besides the rewiring of excitatory circuit, an abnormal depolarizing GABAergic drive has been hypothesized to participate in the epileptogenic processes. However, a remaining clinically relevant question is whether early post Status Epilepticus (SE) evoked chloride dysregulation is important for the remodeling of aberrant glutamatergic neuronal circuit. METHODS: Osmotic mini-pumps were used to infuse intracerebrally a specific inhibitor of depolarizing GABAergic transmission as well as a functionally blocking antibody towards the pan-neurotrophin receptor p75 (p75(NTR) )...
January 11, 2017: Annals of Neurology
https://www.readbyqxmd.com/read/28074478/ultrastructural-analysis-of-parvalbumin-synapses-in-human-dorsolateral-prefrontal-cortex
#17
Jill R Glausier, Rosalinda C Roberts, David A Lewis
Coordinated activity of neural circuitry in the primate dorsolateral prefrontal cortex (DLPFC) supports a range of cognitive functions. Altered DLPFC activation is implicated in a number of human psychiatric and neurological illnesses. Proper DLPFC activity is, in part, maintained by two populations of neurons containing the calcium-binding protein parvalbumin (PV): local inhibitory interneurons that form Type II synapses, and long-range glutamatergic inputs from the thalamus that form Type I synapses. Understanding the contributions of each PV neuronal population to human DLPFC function requires a detailed examination of their anatomical properties...
January 11, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28074469/development-of-cone-photoreceptors-and-their-synapses-in-the-human-and-monkey-fovea
#18
Anita Hendrickson, Chi Zhang
During retinal development, ribbon synapse assembly in the photoreceptors is a crucial step involving numerous molecules. While the developmental sequence of plexiform layers in human retina has been characterized, the molecular steps of synaptogenesis remain largely unknown. In the present study, we focused on the central rod-free region of primate retina, the fovea, to specifically investigate the development of cone photoreceptor ribbon synapses. Immunocytochemistry and electron microscopy were utilized to track the expression of photoreceptor transduction proteins and ribbon and synaptic markers in fetal human and Macaca retina...
January 11, 2017: Journal of Comparative Neurology
https://www.readbyqxmd.com/read/28072412/glutamatergic-and-gabaergic-gene-sets-in-attention-deficit-hyperactivity-disorder-association-to-overlapping-traits-in-adhd-and-autism
#19
J Naaijen, J Bralten, G Poelmans, J C Glennon, B Franke, J K Buitelaar
Attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorders (ASD) often co-occur. Both are highly heritable; however, it has been difficult to discover genetic risk variants. Glutamate and GABA are main excitatory and inhibitory neurotransmitters in the brain; their balance is essential for proper brain development and functioning. In this study we investigated the role of glutamate and GABA genetics in ADHD severity, autism symptom severity and inhibitory performance, based on gene set analysis, an approach to investigate multiple genetic variants simultaneously...
January 10, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28071216/disinhibition-of-the-rat-prelimbic-cortex-promotes-serotonergic-activation-of-the-dorsal-raphe-nucleus-and-panicolytic-like-behavioral-effects
#20
Paula Sm Yamashita, Ailton Spiacci, James E Hassel, Christopher A Lowry, Helio Zangrossi
Several studies have shown that serotonin plays a dual role in the modulation of defensive behaviors related to anxiety and panic. A major source of serotonergic projections to limbic structures responsible for this modulation is the dorsal raphe nucleus (DR). Anatomical studies indicate that the prelimbic (PL) cortex sends dense glutamatergic projections to the DR, leading to stimulation or inhibition of serotonin release in structures innervated by the DR. The objective of the present study was to investigate if GABAergic disinhibition of the PL by means of local administration of picrotoxin (PIC), a chloride channel blocker, can affect serotonergic tone and the expression of defensive behaviors related to anxiety and panic...
January 1, 2017: Journal of Psychopharmacology
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