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https://www.readbyqxmd.com/read/28634445/antioxidant-treatment-with-n-acetyl-cysteine-prevents-the-development-of-cognitive-and-social-behavioral-deficits-that-result-from-perinatal-ketamine-treatment
#1
Aarron Phensy, Hasmik E Duzdabanian, Samantha Brewer, Anurag Panjabi, Christopher Driskill, Annuska Berz, George Peng, Sven Kroener
Alterations of the normal redox state can be found in all stages of schizophrenia, suggesting a key role for oxidative stress in the etiology and maintenance of the disease. Pharmacological blockade of N-methyl-D-aspartic acid (NMDA) receptors can disrupt natural antioxidant defense systems and induce schizophrenia-like behaviors in animals and healthy human subjects. Perinatal administration of the NMDA receptor (NMDAR) antagonist ketamine produces persistent behavioral deficits in adult mice which mimic a range of positive, negative, and cognitive symptoms that characterize schizophrenia...
2017: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/28634070/high-and-low-concentration-of-17%C3%AE-estradiol-protect-cerebellar-granule-neurons-in-different-time-windows
#2
Irene B Sørvik, Ragnhild E Paulsen
17α-estradiol is a hormonally inactive isomer of 17β-estradiol, but with similar potency as neuroprotector. However, we have previously reported that pretreatment with high concentration (10 μM) of both estrogens abolishes their neuroprotection in rat cerebellar granule neurons. Here, we have examined neuroprotective properties of 17α-estradiol against glutamate-induced excitotoxicity in chicken cerebellar granule neurons using low (1 nM) and high concentration.17α-Estradiol, 1 nM, was neuroprotective when glutamate was administered after a pretreatment period of 24 h, but not when coadministered with glutamate...
June 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28632204/successful-pharmacotherapy-for-the-treatment-of-severe-feeding-aversion-with-mechanistic-insights-from-cross-species-neuronal-remodeling
#3
W G Sharp, A G Allen, K H Stubbs, K K Criado, R Sanders, C E McCracken, R G Parsons, L Scahill, S L Gourley
Pediatric feeding disorders affect up to 5% of children, causing severe food intake problems that can result in serious medical and developmental outcomes. Behavioral intervention (BI) is effective in extinguishing feeding aversions, and also expert-dependent, time/labor-intensive and not well understood at a neurobiological level. Here we first conducted a double-blind, placebo-controlled trial comparing BI with BI plus d-cycloserine (DCS). DCS is a partial N-methyl-d-aspartate (NMDA) receptor agonist shown to augment extinction therapies in multiple anxiety disorders...
June 20, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28629864/structure-function-relationships-in-human-d-aspartate-oxidase-characterisation-of-variants-corresponding-to-known-single-nucleotide-polymorphisms
#4
Masumi Katane, Ryo Kanazawa, Risa Kobayashi, Megumi Oishi, Kazuki Nakayama, Yasuaki Saitoh, Tetsuya Miyamoto, Masae Sekine, Hiroshi Homma
D-Aspartate oxidase (DDO) is a degradative enzyme that is stereospecific for the acidic amino acid D-aspartate, an endogenous agonist of the N-methyl-D-aspartate (NMDA) receptor. Dysregulation of NMDA receptor-mediated neurotransmission has been implicated in the onset of various neuropsychiatric disorders including schizophrenia and in chronic pain. Thus, appropriate regulation of the amount of D-aspartate is believed to be important for maintaining proper neural activity in the nervous system. Herein, the effects of the non-synonymous single nucleotide polymorphisms (SNPs) R216Q and S308N on several properties of human DDO were examined...
June 16, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28623767/an-examination-of-the-roles-of-glutamate-and-sex-in-latent-inhibition-relevance-to-the-glutamate-hypothesis-of-schizophrenia
#5
Andrew Chih Wei Huang, Alan Bo-Han He, Chih-Chung Chen
The present study examined the effects of the glutamate receptor antagonist MK-801, the glutamate receptor agonist N-methyl-D-aspartate (NMDA), and sexual dimorphism on latent inhibition to elucidate the glutamate hypothesis of schizophrenia. During the pre-exposure phase, 56 male and 65 female Wistar rats were intracerebroventricularly administered normal saline, MK-801 or NMDA, in the left ventricle and then exposed to a passive avoidance box (or a different context) in three trials over 3 days. Then, all of the rats were placed in the light compartment of the passive avoidance box and were allowed to enter the dark compartment, where they each received a footshock (1mA, 2s) in five trials over 5 days...
June 12, 2017: Psychiatry Research
https://www.readbyqxmd.com/read/28619253/the-n-methyl-d-aspartate-receptor-memory-madness-and-more
#6
Alejandro Ramirez, Melissa R Arbuckle
No abstract text is available yet for this article.
July 1, 2017: Biological Psychiatry
https://www.readbyqxmd.com/read/28616020/minocycline-targets-multiple-secondary-injury-mechanisms-in-traumatic-spinal-cord-injury
#7
REVIEW
Robert B Shultz, Yinghui Zhong
Minocycline hydrochloride (MH), a semi-synthetic tetracycline derivative, is a clinically available antibiotic and anti-inflammatory drug that also exhibits potent neuroprotective activities. It has been shown to target multiple secondary injury mechanisms in spinal cord injury, via its anti-inflammatory, anti-oxidant, and anti-apoptotic properties. The secondary injury mechanisms that MH can potentially target include inflammation, free radicals and oxidative stress, glutamate excitotoxicity, calcium influx, mitochondrial dysfunction, ischemia, hemorrhage, and edema...
May 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28614182/ethanol-alters-n-methyl-d-aspartate-receptor-regulation-in-the-hippocampus-of-adolescent-rats
#8
Ratna Sircar
Our laboratory and others have shown that ethanol disrupts hippocampus-associated memory formation in adolescent rats, but the signaling pathway involved remains largely unknown. Phosphorylation of the N-methyl-D-aspartate receptor, particularly the N-methyl-D-aspartate receptor subunit 2B (NR2B), has been implicated in several ethanol effects and in memory formation. The present study investigated the effects of repeated ethanol exposure on the phosphorylation of the NR2B subunit and src protein in the hippocampus of adolescent rats...
June 13, 2017: Neuroreport
https://www.readbyqxmd.com/read/28612328/antidepressant-actions-of-ketamine-mediated-by-the-mechanistic-target-of-rapamycin-nitric-oxide-and-rheb
#9
REVIEW
Maged M Harraz, Solomon H Snyder
The weeks/months it takes for traditional antidepressants to act pose an obstacle in the management of depression. Ketamine's prompt and sustained antidepressant effects constitute a major advance. Multiple studies implicate glutamatergic signaling to protein synthesis machinery and synapse formation in ketamine's antidepressant effects. Here we review evidence linking ketamine to glutamate receptor subtypes and protein homeostasis. We describe a signaling cascade wherein nitric oxide drives the formation of a ternary protein complex comprised of glyceraldehyde 3-phosphate dehydrogenase, seven in absentia homolog 1, and Ras homolog enriched in brain downstream of the glutamate N-methyl-D-aspartate receptor...
June 13, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/28611597/functional-properties-of-human-nmda-receptors-associated-with-epilepsy-related-mutations-of-glun2a-subunit
#10
Dmitry A Sibarov, Nadine Bruneau, Sergei M Antonov, Pierre Szepetowski, Nail Burnashev, Rashid Giniatullin
Genetic variants of the glutamate activated N-methyl-D-aspartate (NMDA) receptor (NMDAR) subunit GluN2A are associated with the hyperexcitable states manifested by epileptic seizures and interictal discharges in patients with disorders of the epilepsy-aphasia spectrum (EAS). The variants found in sporadic cases and families are of different types and include microdeletions encompassing the corresponding GRIN2A gene as well as nonsense, splice-site and missense GRIN2A defects. They are located at different functional domains of GluN2A and no clear genotype-phenotype correlation has emerged yet...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28611595/mtorc1-is-a-local-postsynaptic-voltage-sensor-regulated-by-positive-and-negative-feedback-pathways
#11
Farr Niere, Kimberly F Raab-Graham
The mammalian/mechanistic target of rapamycin complex 1 (mTORC1) serves as a regulator of mRNA translation. Recent studies suggest that mTORC1 may also serve as a local, voltage sensor in the postsynaptic region of neurons. Considering biochemical, bioinformatics and imaging data, we hypothesize that the activity state of mTORC1 dynamically regulates local membrane potential by promoting and repressing protein synthesis of select mRNAs. Our hypothesis suggests that mTORC1 uses positive and negative feedback pathways, in a branch-specific manner, to maintain neuronal excitability within an optimal range...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28611584/glial-and-neuronal-glutamate-transporters-differ-in-the-na-requirements-for-activation-of-the-substrate-independent-anion-conductance
#12
Christopher B Divito, Jenna E Borowski, Nathan G Glasgow, Aneysis D Gonzalez-Suarez, Delany Torres-Salazar, Jon W Johnson, Susan G Amara
Excitatory amino acid transporters (EAATs) are secondary active transporters of L-glutamate and L- or D-aspartate. These carriers also mediate a thermodynamically uncoupled anion conductance that is gated by Na(+) and substrate binding. The activation of the anion channel by binding of Na(+) alone, however, has only been demonstrated for mammalian EAAC1 (EAAT3) and EAAT4. To date, no difference has been observed for the substrate dependence of anion channel gating between the glial, EAAT1 and EAAT2, and the neuronal isoforms EAAT3, EAAT4 and EAAT5...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28611572/4r-cembranoid-improves-outcomes-after-6-hydroxydopamine-challenge-in-both-in-vitro-and-in-vivo-models-of-parkinson-s-disease
#13
Jing Hu, P A Ferchmin, Ann M Hemmerle, Kim B Seroogy, Vesna A Eterovic, Jiukuan Hao
(1S, 2E, 4R, 6R,-7E, 11E)-2, 7, 11-cembratriene-4, 6-diol (4R) is one of the cembranoids found in tobacco leaves. Previous studies have found that 4R protected acute rat hippocampal slices against neurotoxicity induced by N-methyl-D-aspartate (NMDA) and against the toxic organophosphorus compounds paraoxon and diisopropylfluorophosphate (DFP). Furthermore, in vivo, 4R reduced the infarct size in a rodent ischemic stroke model and neurodegeneration caused by DFP. The present study expanded our previous study by focusing on the effect of 4R in Parkinson's disease (PD) and elucidating its underlying mechanisms using 6-hydroxydopamine (6-OHDA)-induced injury models...
2017: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/28608233/alleviation-by-gabab-receptors-of-neurotoxicity-mediated-by-mitochondrial-permeability-transition-pore-in-cultured-murine-cortical-neurons-exposed-to-n-methyl-d-aspartate
#14
Toshihiko Kinjo, Yoshino Ashida, Hiroshi Higashi, Satoshi Sugimura, Miho Washida, Hiroki Niihara, Kiyokazu Ogita, Yukio Yoneda, Nobuyuki Kuramoto
Mitochondrial permeability transition pore (PTP) is supposed to at least in part participate in molecular mechanisms underlying the neurotoxicity seen after overactivation of N-methyl-D-aspartate (NMDA) receptor (NMDAR) in neurons. In this study, we have evaluated whether activation of GABAB receptor (GABABR), which is linked to membrane G protein-coupled inwardly-rectifying K(+) ion channels (GIRKs), leads to protection of the NMDA-induced neurotoxicity in a manner relevant to mitochondrial membrane depolarization in cultured embryonic mouse cortical neurons...
June 12, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28606234/-efficacy-and-safety-of-cyclophosphamide-as-a-sequential-immunotherapy-drug-for-anti-n-methyl-d-aspartate-receptor-encephalitis-in-children
#15
Wei-Wen Zhu, Wei-Ping Liao, Yong-Hong Yi, Xing-Wang Song
OBJECTIVE: To evaluate the efficacy and safety of cyclophosphamide as a second-line drug in the treatment of children with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. METHODS: Six children with anti-NMDAR encephalitis, who showed poor response to steroids and intravenous immunoglobulin, were given cyclophosphamide as a second-line immunotherapy. Follow-up was performed to evaluate the efficacy and safety of cyclophosphamide. RESULTS: After first-line immunotherapy for 1-4 weeks, the six patients had reduced psychiatric symptoms, seizures, and involuntary movements; three patients had an improved level of consciousness and were able to make simple conversations...
June 2017: Zhongguo Dang Dai Er Ke za Zhi, Chinese Journal of Contemporary Pediatrics
https://www.readbyqxmd.com/read/28604057/heterogeneity-of-d-serine-distribution-in-the-human-central-nervous-system
#16
Masataka Suzuki, Nobuaki Imanishi, Masashi Mita, Kenji Hamase, Sadakazu Aiso, Jumpei Sasabe
D-serine is an endogenous ligand for N-methyl-D-aspartate glutamate receptors. Accumulating evidence including genetic associations of D-serine metabolism with neurological or psychiatric diseases suggest that D-serine is crucial in human neurophysiology. However, distribution and regulation of D-serine in humans are not well understood. Here, we found that D-serine is heterogeneously distributed in the human central nervous system (CNS). The cerebrum contains the highest level of D-serine among the areas in the CNS...
May 2017: ASN Neuro
https://www.readbyqxmd.com/read/28602646/the-effects-of-glycine-on-auditory-mismatch-negativity-in-schizophrenia
#17
Lisa-Marie Greenwood, Sumie Leung, Patricia T Michie, Amity Green, Pradeep J Nathan, Paul Fitzgerald, Patrick Johnston, Nadia Solowij, Jayashri Kulkarni, Rodney J Croft
Glycine increases N-methyl-d-aspartate receptor (NMDAR) mediated glutamatergic function. Mismatch negativity (MMN) is a proposed biomarker of glutamate-induced improvements in clinical symptoms, however, the effect of glycine-mediated NMDAR activation on MMN in schizophrenia is not well understood. This study aimed to determine the effects of acute and 6-week chronic glycine administration on MMN in schizophrenia patients. MMN amplitude was compared at baseline between 22 patients (schizophrenia or schizoaffective disorder; receiving stable antipsychotic medication; multi-centre recruitment) and 21 age- and gender-matched controls...
June 8, 2017: Schizophrenia Research
https://www.readbyqxmd.com/read/28600040/anti-n-methyl-d-aspartate-receptor-nmdar-encephalitis-during-pregnancy-clinical-analysis-of-reported-cases
#18
Yan-Chao Shi, Xiu-Ju Chen, Hong-Mei Zhang, Zhen Wang, Da-Yong Du
OBJECTIVE: To analyze the clinical features of 13 pregnant patients with anti-N-Methyl-d-Aspartate receptor (NMDAR) encephalitis. MATERIALS AND METHODS: Retrospective review of thirteen reported cases was conducted for anti-NMDAR encephalitis patients during pregnancy. The clinical data were collected from papers published in PubMed prior to 16 February 2016. Statistical analysis of the data was performed, which encompasses the patients' age, past medical history, onset of symptoms, concomitant with ovarian teratomas, immunotherapy, outcomes of mothers and newborns...
June 2017: Taiwanese Journal of Obstetrics & Gynecology
https://www.readbyqxmd.com/read/28595035/n-methyl-d-aspartate-receptors-mediate-epilepsy-induced-axonal-impairment-and-tau-phosphorylation-via-activating-glycogen-synthase-kinase-3%C3%AE-and-cyclin-dependent-kinase-5
#19
Xi Liu, Shu Ou, Maojia Yin, Tao Xu, Teng Wang, Ying Liu, Xueying Ding, Xinyuan Yu, Jinxian Yuan, Hao Huang, Xiuhang Zhang, Xinjie Tan, Lifen Chen, Yangmei Chen
The mechanism of epilepsy-induced axonal impairment is poorly understood. N-methyl-D-aspartate receptors (NMDARs) play important roles in epilepsy and mediate structural and functional axonal impairment. GSK-3β and Cdk5 affect axons and are regulated by NMDARs, while their roles in epilepsy-induced axonal impairment are unclear. We demonstrated that axonal impairment is characterized by neurofilament heavy (NFH) reduction, amyloid precursor protein (APP) accumulation, and increased tau phosphorylation accompanied by a decrease of total tau in temporal lobe epilepsy (TLE) patients and pentylenetetrazol (PTZ)-kindled rats...
April 2017: Discovery Medicine
https://www.readbyqxmd.com/read/28593130/the-neuronal-and-astrocytic-protein-slc38a10-transports-glutamine-glutamate-and-aspartate-suggesting-a-role-in-neurotransmission
#20
Sofie V Hellsten, Maria G Hägglund, Mikaela M Eriksson, Robert Fredriksson
In brain cells, glutamine transporters are vital to monitor and control the levels of glutamate and GABA. There are 11 members of the SLC38 family of amino acid transporters of which eight have been functionally characterized. Here, we report the first histological and functional characterization of the previously orphan member, SLC38A10. We used pairwise global sequence alignments to determine the sequence identity between the SLC38 family members. SLC38A10 was found to share 20-25% transmembrane sequence identity with several family members, and was predicted to have 11 transmembrane helices...
June 2017: FEBS Open Bio
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