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Hang Zheng, Hong-Yan Zhu, Xiao-Yu Zhang, Meng Wang, Ying Xiao, Guang-Yin Xu, Xing-Hong Jiang
Hydrogen sulfide (H2S) contributes to visceral hyperalgesia in primary sensory neurons, but its role in central nervous system remains largely unknown. This study was to investigate the roles and underlying mechanisms of H2S and its endogenous synthesis enzymes in the arcuate nucleus (ARC) in rat pancreatic hyperalgesia. Chronic pancreatitis (CP) was induced in male adult Sprague-Dawley rats by intra-pancreatic ductal injection of trinitrobenzene sulfonic acid (TNBS). Abdominal hyperalgesia was assessed by referred somatic behaviors to mechanical stimulation of rat abdomen...
October 25, 2016: Sheng Li Xue Bao: [Acta Physiologica Sinica]
Jillian Iafrati, Arnaud Malvache, Cecilia Gonzalez Campo, M Juliana Orejarena, Olivier Lassalle, Lamine Bouamrane, Pascale Chavis
The postnatal maturation of the prefrontal cortex (PFC) represents a period of increased vulnerability to risk factors and emergence of neuropsychiatric disorders. To disambiguate the pathophysiological mechanisms contributing to these disorders, we revisited the endophenotype approach from a developmental viewpoint. The extracellular matrix protein reelin which contributes to cellular and network plasticity, is a risk factor for several psychiatric diseases. We mapped the aggregate effect of the RELN risk allele on postnatal development of PFC functions by cross-sectional synaptic and behavioral analysis of reelin-haploinsufficient mice...
October 21, 2016: Scientific Reports
Bok Soon Go, Sarah M Barry, Jacqueline F McGinty
Cocaine self-administration induces dysfunctional neuroadaptations in the prefrontal cortex that underlie relapse to cocaine-seeking. Cocaine self-administration disturbs glutamatergic transmission in the nucleus accumbens that is prevented by infusion of brain-derived neurotrophic factor (BDNF) into the prelimbic area of the prefrontal cortex. Intra-prelimbic infusion of BDNF decreases cocaine-seeking in a TrkB-ERK MAP kinase-dependent manner. Neuronal activity triggers an interaction between TrkB receptors and NMDA receptors, leading to ERK activation...
October 17, 2016: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
J Xu, B J Hartley, P Kurup, A Phillips, A Topol, M Xu, C Ononenyi, E Foscue, S-M Ho, T D Baguley, N Carty, C S Barros, U Müller, S Gupta, P Gochman, J Rapoport, J A Ellman, C Pittenger, B Aronow, A C Nairn, M W Nestor, P J Lombroso, K J Brennand
The brain-specific tyrosine phosphatase, STEP (STriatal-Enriched protein tyrosine Phosphatase) is an important regulator of synaptic function. STEP normally opposes synaptic strengthening by increasing N-methyl D-aspartate glutamate receptor (NMDAR) internalization through dephosphorylation of GluN2B and inactivation of the kinases extracellular signal-regulated kinase 1/2 and Fyn. Here we show that STEP61 is elevated in the cortex in the Nrg1(+/-) knockout mouse model of schizophrenia (SZ). Genetic reduction or pharmacological inhibition of STEP prevents the loss of NMDARs from synaptic membranes and reverses behavioral deficits in Nrg1(+/-) mice...
October 18, 2016: Molecular Psychiatry
Erik Nylander, Alfhild Grönbladh, Sofia Zelleroth, Shanti Diwakarla, Fred Nyberg, Mathias Hallberg
Human growth hormone (GH) displays promising protective effects in the central nervous system after damage caused by various insults. Current evidence suggests that these effects may involve N-methyl-d-aspartate (NMDA) receptor function, a receptor that also is believed to play a role in opioid-induced neurotoxicity. The aims of the present study were to examine the acute toxic effects of methadone, an opioid receptor agonist and NMDA receptor antagonist, as well as to evaluate the protective properties of recombinant human GH (rhGH) on methadone-induced toxicity...
October 13, 2016: Neuroscience
Louise K Refsgaard, Darryl S Pickering, Jesper T Andreasen
Evidence suggests that N-methyl-D-aspartate receptor (NMDAR) antagonists could be efficacious in treating depression and anxiety, but side effects constitute a challenge. This study evaluated the antidepressant-like and anxiolytic-like actions, and cognitive and motor side effects of four NMDAR antagonists. MK-801, ketamine, S-ketamine, RO 25-6981 and the positive control, citalopram, were tested for antidepressant-like and anxiolytic-like effects in mice using the forced-swim test, the elevated zero maze and the novelty-induced hypophagia test...
October 12, 2016: Behavioural Pharmacology
Meilin Tian, Shixin Ye
Allostery is essential to neuronal receptor function, but its transient nature poses a challenge for characterization. The N-terminal domains (NTDs) distinct from ligand binding domains are a major locus for allosteric regulation of NMDA receptors (NMDARs), where different modulatory binding sites have been observed. The inhibitor ifenprodil, and related phenylethanoamine compounds specifically targeting GluN1/GluN2B NMDARs have neuroprotective activity. However, whether they use differential structural pathways than the endogenous inhibitor Zn(2+) for regulation is unknown...
October 7, 2016: Scientific Reports
Devesh Mishra, Jose Ignacio Pena-Bravo, Kah-Chung Leong, Antonieta Lavin, Carmela M Reichel
World-wide methamphetamine (meth) use is increasing at a rapid rate; therefore, it has become increasingly important to understand the synaptic changes and neural mechanisms affected by drug exposure. In rodents, 6-h access to contingent meth results in an escalation of drug intake and impaired cognitive sequelae typically associated with changes within the corticostriatal circuitry. There is a dearth of knowledge regarding the underlying physiological changes within this circuit following meth self-administration...
October 5, 2016: Brain Structure & Function
F Woodward Hopf
Addiction to alcohol and drugs is a major social and economic problem, and there is considerable interest in understanding the molecular mechanisms that promote addictive drives. A number of proteins have been identified that contribute to expression of addictive behaviors. NMDA receptors (NMDARs), a subclass of ionotropic glutamate receptors, have been of particular interest because their physiological properties make them an attractive candidate for gating induction of synaptic plasticity, a molecular change thought to mediate learning and memory...
October 5, 2016: Genes, Brain, and Behavior
Małgorzata H Lehner, Ewa Taracha, Ewelina Kaniuga, Aleksandra Wisłowska-Stanek, Marek Gryz, Alicja Sobolewska, Danuta Turzyńska, Anna Skórzewska, Adam Płaźnik
This study utilised the two injection protocol of sensitisation (TIPS) and the conditioned place preference test to validate and extend previous findings on the effects of amphetamine on positive reinforcement-related 50 kHz ultrasonic vocalisation (USV) in rats. We also examined changes in the expression of c-Fos and the NMDA receptor 2B (GluN2B) subunit, markers of neuronal activity and plasticity, in brain regions of rats in response to TIPS. We used low anxiety-responsive (LR) and high anxiety-responsive (HR) rats, which are known to exhibit different fear-conditioned response strengths, different susceptibilities to amphetamine in the TIPS procedure and different amphetamine-dependent 50 kHz USV responses...
October 4, 2016: Journal of Psychopharmacology
Meagan L Auger, Stan B Floresco
NMDA glutamatergic and GABAergic transmission have both been implicated in regulating working memory functions mediated by the prefrontal cortex (PFC), and perturbations in these neurotransmitter systems have been proposed to underlie deficits in these functions observed in schizophrenia. Here, we examined the consequence of disrupting GABAergic or NMDA glutamatergic transmission within the medial PFC of rats on a delayed-response paradigm with translational relevance to working memory tasks used with humans...
September 24, 2016: Neuropharmacology
Noriko Isoo, Takae Ohno, Mutsumi Isowaki, Satoshi Fukuda, Naoyuki Murabe, Hiroaki Mizukami, Keiya Ozawa, Masayoshi Mishina, Masaki Sakurai
Neuronal plasticity is especially active in the young, during short windows of time termed critical periods, and loss of a critical period leads to functional limitations in the adults. The mechanism that governs the length of critical periods remains unknown. Here we show that levels of the NMDA receptor GluN2B subunit, which functions as a Ca(2+) channel, declines in spinal cord synapses toward the end of the critical period for activity-dependent corticospinal synapse elimination. This period could be prolonged by blocking the decline of GluN2B, and after its termination the critical period could be reopened through upregulation of GluN2B...
September 28, 2016: Scientific Reports
Chikako Kaneko, Norshalena Shakespear, Mario Tuchiya, Jin Kubo, Teiji Yamamoto, Soichi Katayama, Yukitoshi Takahashi
Five consecutive cases of anti-NMDA-receptor encephalitis that we encountered were marked by a rapidly fluctuating level of consciousness associated with psychotic and delirious mental states. Opisthotonus, catatonia, and rhythmic and non-rhythmic involuntary movements of the mouth and jaw were also characteristic features of these particular cases. Serious and potentially fatal problems included epilepsia partialis continua, partial and generalized seizures, and respiratory depression, resembling the symptoms of encephalitis lethargica...
September 2016: Brain and Nerve, Shinkei Kenkyū No Shinpo
Andrew J Samson, Graham Robertson, Michele Zagnoni, Christopher N Connolly
Acute secondary neuronal cell death, as seen in neurodegenerative disease, cerebral ischemia (stroke) and traumatic brain injury (TBI), drives spreading neurotoxicity into surrounding, undamaged, brain areas. This spreading toxicity occurs via two mechanisms, synaptic toxicity through hyperactivity, and excitotoxicity following the accumulation of extracellular glutamate. To date, there are no fast-acting therapeutic tools capable of terminating secondary spreading toxicity within a time frame relevant to the emergency treatment of stroke or TBI patients...
2016: Scientific Reports
Riley Edward Perszyk, John O DiRaddo, Katie L Strong, Chian-Ming Low, Kevin K Ogden, Alpa Khatri, Geoffrey A Vargish, Kenneth A Pelkey, Ludovic Tricoire, Dennis C Liotta, Yoland Smith, Chris J McBain, Stephen F Traynelis
NMDA receptors (NMDARs) are ionotropic glutamatergic receptors that have been implicated in learning, development, and neuropathological conditions. They are typically composed of GluN1 and GluN2A-D subunits. Whereas a great deal is known about the role of GluN2A- and GluN2B-containing NMDARs, much less is known about GluN2D-containing NMDARs. Here we explore the subunit composition of synaptic NMDARs on hippocampal interneurons. GluN2D mRNA was detected by single-cell PCR and in situ hybridization in diverse interneuron subtypes in the CA1 region of the hippocampus...
September 13, 2016: Molecular Pharmacology
Atsuko Kimura, Kazuhiko Namekata, Xiaoli Guo, Chikako Harada, Takayuki Harada
Glaucoma is a neurodegenerative disease of the eye and it is one of the major causes of blindness. Glaucoma is usually associated with elevated intraocular pressure (IOP) and the current therapy focuses on reduction of IOP. However, neuroprotective strategies could also be beneficial for treatment of glaucoma because the pathology of the disease involves retinal ganglion cell (RGC) death and damage to the optic nerve. Dedicator of cytokinesis 3 (Dock3) is an atypical guanine exchange factor (GEF) that belongs to a family of Dock proteins, Dock1-11...
September 9, 2016: Histology and Histopathology
Wen-Bo Kang, Qi Yang, Yan-Yan Guo, Lu Wang, Dong-Sheng Wang, Qiang Cheng, Xiao-Ming Li, Jun Tang, Jian-Ning Zhao, Gang Liu, Min Zhuo, Ming-Gao Zhao
BACKGROUND: Cancer pain, especially the one caused by metastasis in bones, is a severe type of pain. Pain becomes chronic unless its causes and consequences are resolved. With improvements in cancer detection and survival among patients, pain has been considered as a great challenge because traditional therapies are partially effective in terms of providing relief. Cancer pain mechanisms are more poorly understood than neuropathic and inflammatory pain states. Chronic inflammatory pain and neuropathic pain are influenced by NB001, an adenylyl cyclase 1 (AC1)-specific inhibitor with analgesic effects...
2016: Molecular Pain
Madhavan Mayadevi, Kesavan Lakshmi, Sudarsana Devi Suma Priya, Sebastian John, Ramakrishnapillai V Omkumar
Interaction of CaMKII and the GluN2B subunit of NMDA receptor is essential for synaptic plasticity events such as LTP. Synaptic targeting of CaMKII and regulation of its biochemical functions result from this interaction. GluN2B binding to the T-site of CaMKII leads to changes in substrate binding and catalytic parameters and inhibition of its own dephosphorylation. We find that CaMKIINα, a natural inhibitor that binds to the T-site of CaMKII, also causes inhibition of dephosphorylation of CaMKII similar to GluN2B...
2016: PloS One
Yukitoshi Takahashi, Takashi Matsudaira, Hitoshi Nakano, Hirosato Nasu, Hitoshi Ikeda, Kentaro Nakaoka, Rumiko Takayama, Masayasu Oota
In 32 patients with prolonged central nervous system symptoms after human papillomavirus (HPV) vaccination, we measured conventional and immunological markers in cerebrospinal fluid (CSF) and compared with the levels in disease controls. Our studies revealed significantly decreased chloride and neuron-specific enolase (NSE) levels in CSF of patients with CNS symptoms after HPV vaccination compared to disease controls. IL-4, IL-13, and CD4(+) T cells increased significantly in patients, and IL-17 increased significantly from 12 to 24months after symptom onset...
September 15, 2016: Journal of Neuroimmunology
Roopashri Holehonnur, Aarron J Phensy, Lily J Kim, Milica Milivojevic, Dat Vuong, Delvin K Daison, Saira Alex, Michael Tiner, Lauren E Jones, Sven Kroener, Jonathan E Ploski
UNLABELLED: Reconsolidation updating is a form of memory modification in which an existing memory can become destabilized upon retrieval and subsequently be modified via protein-synthesis-dependent reconsolidation. However, not all memories appear to destabilize upon retrieval and thus are not modifiable via reconsolidation updating approaches and the neurobiological basis for this remains poorly understood. Here, we report that auditory fear memories created with 10 tone-shock pairings are resistant to retrieval-dependent memory destabilization and are associated with an increase in the synaptic GluN2A/GluN2B ratio in neurons of the basal and lateral amygdala (BLA) compared with weaker fear memories created via one or three tone-shock pairings...
September 7, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
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