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https://www.readbyqxmd.com/read/29772491/calpain-inhibition-reduces-nmda-receptor-rundown-in-rat-substantia-nigra-dopamine-neurons
#1
Jerry Zhao, Michel Baudry, Susan Jones
Repeated activation of N-Methyl-d-aspartate receptors (NMDARs) causes a Ca2+ -dependent reduction in NMDAR-mediated current in dopamine (DA) neurons of the substantia nigra pars compacta (SNc) in one week old rats; however, a Ca2+ -dependent regulatory protein has not been identified. The role of the Ca2+ -dependent cysteine protease, calpain, in mediating NMDAR current rundown was investigated. In brain slices from rats aged postnatal day 7-9 ('P7'), bath application of either of the membrane permeable calpain inhibitors, N-Acetyl-L-leucyl-L-leucyl-L-norleucinal (ALLN, 20 μM) or MDL-28170 (30 μM) significantly reduced whole-cell NMDAR current rundown...
May 4, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29771431/study-of-molecular-mechanisms-of-learning-and-memory-impairment-in-neonatal-rats-post-intrauterine-distress-via-the-pathway-of-tau-protein-hyperphosphorylation
#2
X-S Wang, H Huang
OBJECTIVE: To explore the reversion of the excitatory amino acid receptor antagonists against the impairment of learning-memory and the hyperphosphorylation of protein Tau induced by fetal intrauterine distress in neonatal rats. MATERIALS AND METHODS: The analysis of variance of factorial design set up two intervention factors, fetal intrauterine distress (two levels: no fetal intrauterine distress and a course of fetal intrauterine distress) and the excitatory amino acid receptor antagonists (three levels: Saline; NMDA receptor antagonist MK-801; astragalosides)...
May 2018: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29768996/a-systematic-review-on-donepezil-based-derivatives-as-potential-cholinesterase-inhibitors-for-alzheimer-s-disease
#3
Jan Korabecny, Katarina Spilovska, Eva Mezeiova, Ondrej Benek, Radomir Juza, Daniel Kaping, Ondrej Soukup
Alzheimer's disease (AD) is a multifactorial progressive neurodegenerative disorder characterized by memory loss, disorientation, and gradual deterioration of intellectual capacity. Its etiology has not been elucidated yet. To date, only one therapeutic approach has been approved for the treatment of AD. The pharmacotherapy of AD has relied on non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist - memantine, and acetylcholinesterase (AChE) inhibitors (AChEIs) - tacrine, donepezil, rivastigmine and galantamine...
May 16, 2018: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/29767953/pharmacological-and-electrophysiological-characterization-of-novel-nmda-receptor-antagonists
#4
Rosana Leiva, Matthew B Phillips, Andreea Larisa Turcu, Esther Gratacòs-Batlle, Lara León-García, Francesc X Sureda, David Soto, Jon W Johnson, Santiago Vazquez
This work reports the synthesis, and pharmacological and electrophysiological evaluation of new N-methyl-D-aspartic acid receptor (NMDAR) channel blocking antagonists featuring polycyclic scaffolds. Changes in the chemical structure modulate the potency and voltage dependence of inhibition. Two of the new antagonists display properties comparable to those of memantine, a clinically approved NMDAR antagonist.
May 16, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29766293/nmda-receptor-subunits-change-in-the-prefrontal-cortex-of-pure-opioid-and-multi-drug-abusers-a-post-mortem-study
#5
Hamidreza Daneshparvar, Mitra-Sadat Sadat-Shirazi, Monir Fekri, Solmaz Khalifeh, Ali Ziaie, Nasrin Esfahanizadeh, Nasim Vousooghi, Mohammad-Reza Zarrindast
Addiction is a chronic relapsing disorder and is one of the most important issues in the world. Changing the level of neurotransmitters and the activities of their receptors, play a major role in the pathophysiology of substance abuse disorders. It is well-established that N-methyl-D-aspartate receptors (NMDARs) play a significant role in the molecular basis of addiction. NMDAR has two obligatory GluN1 and two regionally localized GluN2 subunits. This study investigated changes in the protein level of GluN1, GluN2A, and GluN2B in the prefrontal cortex of drug abusers...
May 16, 2018: European Archives of Psychiatry and Clinical Neuroscience
https://www.readbyqxmd.com/read/29766040/the-midline-axon-crossing-decision-is-regulated-through-an-activity-dependent-mechanism-by-the-nmda-receptor
#6
Jingxia Gao, Tamara J Stevenson, Adam D Douglass, Joshua P Barrios, Joshua L Bonkowsky
Axon guidance in vertebrates is controlled by genetic cascades as well as by intrinsic activity-dependent refinement of connections. Midline axon crossing is one of the best studied pathfinding models and is fundamental to the establishment of bilaterally symmetric nervous systems. However, it is not known whether crossing requires intrinsic activity in axons, and what controls that activity. Further, a mechanism linking neuronal activity and gene expression has not been identified for axon pathfinding. Using embryonic zebrafish, we found that the NMDA receptor (NMDAR) NR1...
March 2018: ENeuro
https://www.readbyqxmd.com/read/29764453/ampa-ergic-regulation-of-amyloid-%C3%AE-levels-in-an-alzheimer-s-disease-mouse-model
#7
Jane C Hettinger, Hyo Lee, Guojun Bu, David M Holtzman, John R Cirrito
BACKGROUND: Extracellular aggregation of the amyloid-β (Aβ) peptide into toxic multimers is a key event in Alzheimer's disease (AD) pathogenesis. Aβ aggregation is concentration-dependent, with higher concentrations of Aβ much more likely to form toxic species. The processes that regulate extracellular levels of Aβ therefore stand to directly affect AD pathology onset. Studies from our lab and others have demonstrated that synaptic activity is a critical regulator of Aβ production through both presynaptic and postsynaptic mechanisms...
May 15, 2018: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/29763637/neurosteroid-pregnenolone-sulfate-alone-and-as-augmentation-of-lurasidone-or-tandospirone-rescues-phencyclidine-induced-deficits-in-cognitive-function-and-social-interaction
#8
L Rajagopal, D Soni, H Y Meltzer
BACKGROUND: Pregnenolone sulfate (PregS), an endogenous neurosteroid, which negatively and positively modulates gamma amino butyric acid subunit A (GABAA ) and N-methyl D-aspartate (NMDA) receptors (R) respectively, among other potential neuroplastic changes on synaptic processes, has shown some beneficial effects on treating cognitive impairment associated with schizophrenia (CIAS) and negative symptoms. Lurasidone (Lur), an atypical antipsychotic drug (AAPD), and tandospirone (Tan), a 5-HT1A  R partial agonist, have also been reported to improve cognitive or negative symptoms, or both, in some schizophrenia patients...
May 12, 2018: Behavioural Brain Research
https://www.readbyqxmd.com/read/29763633/estradiol-induced-enhancement-of-fear-extinction-in-female-rats-the-role-of-nmda-receptor-activation
#9
Bronwyn M Graham, Elliot Scott
Converging cross-species evidence indicates that fear extinction (the laboratory basis of exposure therapy for anxiety disorders) in females is modulated by endogenous and exogenous estradiol. The mechanisms underlying estradiol's influences on fear extinction are largely undefined. However, one likely candidate is the NMDA-receptor (NMDAr), activation of which is necessary for estradiol-mediated enhancements in structural and functional neural plasticity, as well as extinction consolidation in males. Here, we demonstrate that systemic co-administration of the non-competitive NMDAr antagonist, MK801, blocked the enhancement of fear extinction by systemic estradiol in ovariectomized rats...
May 12, 2018: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/29761580/cross-modal-restoration-of-ocular-dominance-plasticity-in-adult-mice
#10
Manuel Teichert, Marcel Isstas, Yitong Zhang, Jürgen Bolz
The temporal closure of one eye in juvenile and young adult mice induces a shift of the ocular dominance (OD) of neurons in the binocular visual cortex. However, OD-plasticity typically declines with age and is completely absent in matured mice beyond postnatal day (PD) 110. As it has been shown that the deprivation of one sensory input can induce neuronal alterations in non-deprived sensory cortices, we here investigated whether cross-modal interactions have the potential to reinstall OD-plasticity in matured mice...
May 14, 2018: European Journal of Neuroscience
https://www.readbyqxmd.com/read/29761122/bortezomib-treatment-for-severe-refractory-anti-nmda-receptor-encephalitis
#11
Yong-Won Shin, Soon-Tae Lee, Tae-Joon Kim, Jin-Sun Jun, Kon Chu
Objective: To evaluate the therapeutic potential of bortezomib, a proteasome inhibitor that target plasma cells, in order to revive stalled recovery in patients with anti- N -methyl-d-aspartate (NMDA) receptor encephalitis who remain bedridden even after aggressive immunotherapy. Methods: We consecutively enrolled patients with anti-NMDA receptor encephalitis who remained bedridden after first-line immunotherapy (steroids and intravenous immunoglobulin), second-line immunotherapy (rituximab), and tocilizumab treatment, and treated them with subcutaneous bortezomib...
May 2018: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/29760525/two-distinct-mechanisms-for-experience-dependent-homeostasis
#12
Michelle C D Bridi, Roberto de Pasquale, Crystal L Lantz, Yu Gu, Andrew Borrell, Se-Young Choi, Kaiwen He, Trinh Tran, Su Z Hong, Andrew Dykman, Hey-Kyoung Lee, Elizabeth M Quinlan, Alfredo Kirkwood
Models of firing rate homeostasis such as synaptic scaling and the sliding synaptic plasticity modification threshold predict that decreasing neuronal activity (for example, by sensory deprivation) will enhance synaptic function. Manipulations of cortical activity during two forms of visual deprivation, dark exposure (DE) and binocular lid suture, revealed that, contrary to expectations, spontaneous firing in conjunction with loss of visual input is necessary to lower the threshold for Hebbian plasticity and increase miniature excitatory postsynaptic current (mEPSC) amplitude...
May 14, 2018: Nature Neuroscience
https://www.readbyqxmd.com/read/29760178/region-and-activity-dependent-regulation-of-extracellular-glutamate
#13
Nawrin F Pinky, Crystal M Wilkie, Jocelyn R Barnes, Matthew P Parsons
Transporter-mediated glutamate uptake plays an essential role in shaping synaptic neurotransmission. The rapid removal of synaptically-released glutamate ensures the high temporal dynamics characteristic of fast excitatory chemical neurotransmission and prevents the overexcitation of extrasynaptic NMDA receptors that have been implicated in synaptic plasticity impairments and cell death. Despite clear regional differences in plasticity and excitotoxic thresholds, few studies have compared extracellular glutamate dynamics across different brain regions and in response to a range of neural activity including plasticity-inducing stimuli...
May 14, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/29759996/pearls-oy-sters-relapse-of-anti-nmda-receptor-encephalitis-after-prior-first-and-second-line-immunotherapy
#14
Sharon Chiang, Tanu Garg, Austin Hu, Hitha Amin, Alfredo Davalos-Balderas, Isabel Alfradique-Dunham, Corey E Goldsmith
No abstract text is available yet for this article.
May 15, 2018: Neurology
https://www.readbyqxmd.com/read/29758384/disruption-of-shp1-nmda-receptor-signaling-in-spinal-cord-dorsal-horn-alleviated-inflammatory-pain
#15
Li Yang, Hu-Hu Bai, Zi-Yang Zhang, Jiang-Ping Liu, Zhan-Wei Suo, Xian Yang, Xiao-Dong Hu
Src-homology 2 domain-containing protein tyrosine phosphatase-1 (SHP1) is one of the non-receptor-like phosphatases that are highly enriched in hematopoietic cells. Although accumulating evidence has implicated the protein tyrosine phosphatases in the regulation of nociceptive transmission and plasticity, it is largely unknown whether SHP1 was expressed in pain-related spinal cord dorsal horn and engaged in the synaptic modification of nociceptive signals. Here we found that SHP1 was present in spinal neurons of rats and functionally coupled to GluN2A subunit-containing N-methyl-d-aspartate subtype of glutamate receptors, one of the key players in central sensitization of nociceptive behaviors...
April 30, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29756080/-de-novo-mutations-and-rare-variants-occurring-in-nmda-receptors
#16
Wenshu XiangWei, Yuwu Jiang, Hongjie Yuan
A significant number of variants/mutations in the N -methyl-D -aspartate glutamatergic receptor (NMDAR) gene family ( GRIN ) have been identified along with stunning advances in the technologies of next generation of whole-exome sequencing. Mutations in human GRIN genes are distributed throughout the entire gene, from amino terminal domain to C-terminal domain, in patients with various neuropsychiatric disorders, including autism spectrum disorders, epilepsy, intellectual disability, attention deficit hyperactivity disorder, and schizophrenia...
April 2018: Current Opinion in Physiology
https://www.readbyqxmd.com/read/29753795/non-anesthetic-effects-of-ketamine-a-review-article-authors-%C3%A2-%C3%A2-%C3%A2-%C3%A2-%C3%A2-%C3%A2-%C3%A2
#17
REVIEW
Jabril Eldufani, Alireza Nekoui, Gilbert Blaise
Ketamine is considered a dissociative anesthetic medication, and it is a commonly administered by a parenteral route. It works mainly by blocking the N-methyl-D-aspartate (NMDA) receptor. It inhibits the voltage-gated Na_ and K_ channels and serotonin and dopamine re-uptake; also, it affects specific receptors, such as α-amino-3-hydroxy-5-methyl-4- isoxazolepropionic acid (AMPA), kainate and aminobutyric acid A receptors. Ketamine appears to have particular mechanisms that are potentially involved during analgesic induction, including enhancing of descending inhibition and anti-inflammatory effects...
May 10, 2018: American Journal of Medicine
https://www.readbyqxmd.com/read/29751228/prenatal-nicotine-exposure-alters-postsynaptic-ampa-receptors-and-glutamate-neurotransmission-within-the-laterodorsal-tegmentum-ldt-of-juvenile-mice
#18
Filip S Polli, Kristi A Kohlmeier
Despite dissemination of information regarding the harm on fetal development of smoking while pregnant, the number of pregnancies associated with nicotine exposure appears to have stagnated. Presence of nicotine during neural formulation is associated with a higher susceptibility of drug dependence, suggesting an altered development of neurons in circuits involved in saliency and motivation. The laterodorsal tegmental nucleus (LDT) plays a role in coding stimuli valence via afferents to mesolimbic nuclei. Accordingly, alterations in development of neural mechanisms in the LDT could be involved in vulnerability to drug dependency...
April 25, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29750883/involvement-of-the-periaqueductal-gray-in-the-descending-antinociceptive-effect-induced-by-the-central-nucleus-of-amygdala
#19
N Bourbia, A Pertovaara
Here we studied whether descending control of mechanical nociception by glutamate in the central nucleus of the amygdala (CeA) of healthy control animals is induced by amygdaloid NMDA receptors and relayed through the midbrain periaqueductal gray (PAG). Mechanical nociception in the hind paws was assessed in rats with chronic guide cannulae for glutamate administration in the right CeA and for inducing local anesthesia in the PAG. In a separate electrophysiological study, ON-like PAG neurons giving an excitatory response to noxious pinch of the tail were recorded in anesthetized rats following glutamate administration into the CeA...
May 10, 2018: Physiological Research
https://www.readbyqxmd.com/read/29749988/amelioration-of-pentylenetetrazole-induced-seizures-by-modulators-of-sigma-n-methyl-d-aspartate-and-ryanodine-receptors-in-mice
#20
Mojtaba Keshavarz, Behdad Yekzaman
Background: Sigma receptors, N-methyl-D-aspartate (NMDA) antagonist, and modulators of intracellular calcium may be useful for seizure control. Therefore, we aimed to evaluate the antiepileptic effects of opipramol, a sigma receptor agonist, against pentylenetetrazole (PTZ)-induced seizures in mice and assess ketamine and caffeine interaction with the antiepileptic effects of opipramol. Methods: PTZ (100 mg/kg) was used for the induction of seizure in 72 male albino Swiss strain of mice (n=8)...
March 2018: Iranian Journal of Medical Sciences
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