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https://www.readbyqxmd.com/read/28212175/advances-in-epilepsy-gene-discovery-and-implications-for-epilepsy-diagnosis-and-treatment
#1
Joseph D Symonds, Sameer M Zuberi, Michael R Johnson
PURPOSE OF REVIEW: Epilepsy genetics is shifting from the academic pursuit of gene discovery to a clinical discipline based on molecular diagnosis and stratified medicine. We consider the latest developments in epilepsy genetics and review how gene discovery in epilepsy is influencing the clinical classification of epilepsy and informing new therapeutic approaches and drug discovery. RECENT FINDINGS: Recent studies highlighting the importance of mutation in GABA receptors, NMDA receptors, potassium channels, G-protein coupled receptors, mammalian target of rapamycin pathway and chromatin remodeling are discussed...
February 15, 2017: Current Opinion in Neurology
https://www.readbyqxmd.com/read/28212107/rheb-in-neuronal-degeneration-regeneration-and-connectivity
#2
Veena Nambiar Potheraveedu, Miriam Schöpel, Raphael Stoll, Rolf Heumann
The small GTPase Rheb was originally detected as an immediate early response protein whose expression was induced by NMDA-dependent synaptic activity in the brain. Rheb's activity is highly regulated by its GTPase activating protein (GAP), the tuberous sclerosis complex protein, which stimulates the conversion from the active, GTP-loaded into the inactive, GDP-loaded conformation. Rheb has been established as an evolutionarily conserved molecular switch protein regulating cellular growth, cell volume, cell cycle, autophagy, and amino acid uptake...
February 17, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28210212/differential-behavioral-and-neurobiological-effects-of-chronic-corticosterone-treatment-in-adolescent-and-adult-rats
#3
Jitao Li, Xiaomeng Xie, Youhong Li, Xiao Liu, Xuemei Liao, Yun-Ai Su, Tianmei Si
Adolescence is a critical period with ongoing maturational processes in stress-sensitive systems. While adolescent individuals show heightened stress-induced hormonal responses compared to adults, it is unclear whether and how the behavioral and neurobiological consequences of chronic stress would differ between the two age groups. Here we address this issue by examining the effects of chronic exposure to the stress hormone, corticosterone (CORT), in both adolescent and adult animals. Male Sprague-Dawley (SD) rats were injected intraperitoneally with CORT (40 mg/kg) or vehicle for 21 days during adolescence (post-natal day (PND) 29-49) or adulthood (PND 71-91) and then subjected to behavioral testing or sacrifice for western blot analyses...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28210211/app-as-a-protective-factor-in-acute-neuronal-insults
#4
REVIEW
Dimitri Hefter, Andreas Draguhn
Despite its key role in the molecular pathology of Alzheimer's disease (AD), the physiological function of amyloid precursor protein (APP) is unknown. Increasing evidence, however, points towards a neuroprotective role of this membrane protein in situations of metabolic stress. A key observation is the up-regulation of APP following acute (stroke, cardiac arrest) or chronic (cerebrovascular disease) hypoxic-ischemic conditions. While this mechanism may increase the risk or severity of AD, APP by itself or its soluble extracellular fragment APPsα can promote neuronal survival...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28209726/therapeutic-targeting-of-the-pathological-triad-of-extrasynaptic-nmda-receptor-signaling-in-neurodegenerations
#5
REVIEW
Hilmar Bading
Activation of extrasynaptic N-methyl-d-aspartate (NMDA) receptors causes neurodegeneration and cell death. The disease mechanism involves a pathological triad consisting of mitochondrial dysfunction, loss of integrity of neuronal structures and connectivity, and disruption of excitation-transcription coupling caused by CREB (cyclic adenosine monophosphate-responsive element-binding protein) shut-off and nuclear accumulation of class IIa histone deacetylases. Interdependency within the triad fuels an accelerating disease progression that culminates in failure of mitochondrial energy production and cell loss...
February 16, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28208013/sex-differences-in-autism-like-behavioral-phenotypes-and-postsynaptic-receptors-expression-in-the-prefrontal-cortex-of-tert-transgenic-mice
#6
Ki Chan Kim, Kyu Suk Cho, Sung Min Yang, Edson Luck Gonzales, Schley Valencia, Pyeong Hwa Eun, Chang Soon Choi, Darine Froy Mabunga, Ji-Woon Kim, Judy Kyoungju Noh, Hee Jin Kim, Se Jin Jeon, Seol-Heui Han, Geon Ho Bahn, Chan Young Shin
Autism spectrum disorder (ASD) remains unexplained and untreated despite the high attention of research in recent years. Aside from its various characteristics is the baffling male preponderance over the female population. Using a validated animal model of ASD which is the telomerase reverse transcriptase overexpressing mice (TERT-tg), we conducted ASD-related behavioral assessments and protein expression experiments to mark the difference between male and females of this animal model. After statistically analyzing the results, we found significant effects of TERT overexpression in sociability, social novelty preference, anxiety, nest building, and electroseizure threshold in the males but not their female littermates...
February 17, 2017: Biomolecules & Therapeutics
https://www.readbyqxmd.com/read/28204809/ketamine-suppresses-the-substance-p-induced-production-of-il-6-and-il-8-by-human-u373mg-glioblastoma-astrocytoma-cells
#7
Keisuke Yamaguchi, Seiichiro Kumakura, Taisuke Murakami, Akimasa Someya, Eiichi Inada, Isao Nagaoka
The neuropeptide substance P (SP) is an important mediator of neurogenic inflammation within the central and peripheral nervous systems. SP has been shown to induce the expression of pro-inflammatory cytokines implicated in the pathogenesis of several disorders of the human brain via the neurokinin-1 receptor (NK-1R). Ketamine, an intravenous anesthetic agent, functions as a competitive antagonist of the excitatory neurotransmission N-methyl-D‑aspartate (NMDA) receptor, and also antagonizes the NK-1R by interfering with the binding of SP...
February 3, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28203201/modulation-of-synaptic-plasticity-in-the-cortex-needs-to-understand-all-the-players
#8
REVIEW
Claire N J Meunier, Pascal Chameau, Philippe M Fossier
The prefrontal cortex (PFC) is involved in cognitive tasks such as working memory, decision making, risk assessment and regulation of attention. These functions performed by the PFC are supposed to rely on rhythmic electrical activity generated by neuronal network oscillations determined by a precise balance between excitation and inhibition balance (E/I balance) resulting from the coordinated activities of recurrent excitation and feedback and feedforward inhibition. Functional alterations in PFC functions have been associated with cognitive deficits in several pathologies such as major depression, anxiety and schizophrenia...
2017: Frontiers in Synaptic Neuroscience
https://www.readbyqxmd.com/read/28203147/astrocyte-dependent-slow-inward-currents-sics-participate-in-neuromodulatory-mechanisms-in-the-pedunculopontine-nucleus-ppn
#9
Adrienn Kovács, Balázs Pál
Slow inward currents (SICs) are known as excitatory events of neurons caused by astrocytic glutamate release and consequential activation of neuronal extrasynaptic NMDA receptors. In the present article we investigate the role of these astrocyte-dependent excitatory events on a cholinergic nucleus of the reticular activating system (RAS), the pedunculopontine nucleus (PPN). It is well known about this and other elements of the RAS, that they do not only give rise to neuromodulatory innervation of several areas, but also targets neuromodulatory actions from other members of the RAS or factors providing the homeostatic drive for sleep...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28202787/dysregulated-glycine-signaling-contributes-to-increased-impulsivity-during-protracted-alcohol-abstinence
#10
Cristina Irimia, Matthew W Buczynski, Luis A Natividad, Sarah A Laredo, Nathaniel Avalos, Loren H Parsons
Persons with alcoholism who are abstinent exhibit persistent impairments in the capacity for response inhibition, and this form of impulsivity is significantly associated with heightened relapse risk. Brain-imaging studies implicate aberrant prefrontal cortical function in this behavioral pathology, although the underlying mechanisms are not understood. Here we present evidence that deficient activation of glycine and serine release in the ventral medial prefrontal cortex (vmPFC) contributes to increased motor impulsivity during protracted abstinence from long-term alcohol exposure...
February 15, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28202572/differential-regulation-of-nmda-receptors-by-d-serine-and-glycine-in-mammalian-spinal-locomotor-networks
#11
David Acton, Gareth Brian Miles
Activation of N-methyl-D-aspartate receptors (NMDARs) requires the binding of a co-agonist, either D-serine or glycine, in addition to glutamate. Changes in occupancy of the co-agonist binding site are proposed to modulate neural networks including those controlling swimming in frog tadpoles. Here, we characterize regulation of the NMDAR co-agonist binding site in mammalian spinal locomotor networks. Blockade of NMDARs by D(-)-2-amino-5-phosphonopentanoic acid (D-APV) or 5,7-dichlorokynurenic acid reduced the frequency and amplitude of pharmacologically induced locomotor-related activity recorded from the ventral roots of spinal-cord preparations from neonatal mice...
February 15, 2017: Journal of Neurophysiology
https://www.readbyqxmd.com/read/28202503/vitamin-d-and-depression-cellular-and-regulatory-mechanisms
#12
REVIEW
Michael J Berridge
Depression is caused by a change in neural activity resulting from an increase in glutamate that drives excitatory neurons and may be responsible for the decline in the activity and number of the GABAergic inhibitory neurons. This imbalance between the excitatory and inhibitory neurons may contribute to the onset of depression. At the cellular level there is an increase in the concentration of intracellular Ca(2+) within the inhibitory neurons that is driven by an increase in entry through the NMDA receptors (NMDARs) and through activation of the phosphoinositide signaling pathway that generates inositol trisphosphate (InsP3) that releases Ca(2+) from the internal stores...
April 2017: Pharmacological Reviews
https://www.readbyqxmd.com/read/28202437/oscillation-patterns-are-enhanced-and-firing-threshold-is-lowered-in-medullary-respiratory-neuron-discharges-by-threshold-doses-of-a-%C3%AE-opioid-receptor-agonist
#13
Peter M Lalley, Steve W Mifflin
μ-Opioid receptors are distributed widely in the brainstem respiratory network, and opioids with selectivity for μ-type receptors slow in-vivo respiratory rhythm in lowest effective doses. Several studies have reported μ-opioid receptor effects on the three-phase rhythm of respiratory neurons, but there are until now no reports of opioid effects on oscillatory activity within respiratory discharges. In this study, effects of the μ-opioid receptor agonist fentanyl on spike train discharge properties of several different types of rhythm-modulating medullary respiratory neuron discharges were analyzed...
February 15, 2017: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/28202296/psychosis-in-the-ed-a-case-of-nmda-receptor-antibody-encephalitis
#14
Joseph Fisher, Clifford Ellingson, Noah Tolby
Anti-N-methyl-d-aspartate antibody receptor (NMDAR) encephalitis is a newly recognized disease increasing in diagnostic frequency. A 27-year-old female presented with symptoms of oral dyskinesia, tachycardia, and altered mental status following a three-month history of depression, lethargy, catatonia, and auditory hallucinations. We utilized our facilities neurology and psychiatry consult services, performed a lumbar puncture (LP), and requested NMDAR antibody titers. Following admission the Anti-NMDAR antibody titer was elevated warranting treatment with intravenous immunoglobulin (IVIG), corticosteroids, and later rituximab...
February 6, 2017: American Journal of Emergency Medicine
https://www.readbyqxmd.com/read/28199666/the-role-of-dopamine-d1-and-d3-receptors-in-n-methyl-d-aspartate-nmda-glycineb-site-regulated-complex-cognitive-behaviors-following-repeated-morphine-administration
#15
Yunpeng Wang, Fangyuan Yin, Hao Guo, Jing Zhang, Peng Yan, Jianghua Lai
No abstract text is available yet for this article.
February 11, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28199019/the-role-of-drebrin-in-neurons
#16
REVIEW
Tomoaki Shirao, Kenji Hanamura, Noriko Koganezawa, Yuta Ishizuka, Hiroyuki Yamazaki, Yuko Sekino
Drebrin is an actin-binding protein that changes the helical pitch of actin filaments (F-actin), and drebrin-decorated F-actin shows slow treadmilling and decreased rate of depolymerization. Moreover, the characteristic morphology of drebrin-decorated F-actin enables it to respond differently to the same signals from other actin cytoskeletons. Drebrin consists of two major isoforms, drebrin E and drebrin A. In the developing brain, drebrin E appears in migrating neurons and accumulates in the growth cones of axons and dendrites...
February 15, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28198441/pdi-regulates-seizure-activity-via-nmda-receptor-redox-in-rats
#17
Ji Yang Kim, Ah-Rhem Ko, Hye-Won Hyun, Su-Ji Min, Ji-Eun Kim
Redox modulation of cysteine residues is one of the post-translational modifications of N-methyl-D-aspartate receptor (NMDAR). Protein disulfide isomerases (PDI), an endoplasmic reticulum (ER) chaperone, plays a crucial role in catalyzing disulfide bond formation, reduction, and isomerization. In the present study, we found that PDI bound to NMDAR in the normal hippocampus, and that this binding was increased in chronic epileptic rats. In vitro thiol reductase assay revealed that PDI increased the amount of thiols on full-length recombinant NR1 protein...
February 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28198211/both-n-methyl-d-aspartate-and-non-n-methyl-d-aspartate-glutamate-receptors-in-the-bed-nucleus-of-the-stria-terminalis-modulate-the-cardiovascular-responses-to-acute-restraint-stress-in-rats
#18
Mariane B Adami, Lucas Barretto-de-Souza, Josiane O Duarte, Jeferson Almeida, Carlos C Crestani
The bed nucleus of the stria terminalis (BNST) is a forebrain structure that has been implicated on cardiovascular responses evoked by emotional stress. However, the local neurochemical mechanisms mediating the BNST control of stress responses are not fully described. In our study we investigated the involvement of glutamatergic neurotransmission within the BNST in cardiovascular changes evoked by acute restraint stress in rats. For this study, we investigated the effects of bilateral microinjections of selective antagonists of either N-methyl-D-aspartate (NMDA) or non-NMDA glutamate receptors into the BNST on the arterial pressure and heart rate increase and the decrease in tail skin temperature induced by acute restraint stress...
February 1, 2017: Journal of Psychopharmacology
https://www.readbyqxmd.com/read/28197902/neuropsychiatric-effects-of-antimicrobial-agents
#19
REVIEW
Nicholas Zareifopoulos, George Panayiotakopoulos
Antimicrobial drugs used in clinical practice are selected on the basis of their selective toxicity against bacterial cells. However, all exhibit multiple offsite interactions with eukaryotic cell structures, resulting in adverse reactions during antimicrobial pharmacotherapy. A multitude of these side effects involve the nervous system as antimicrobials at clinically relevant concentrations seem to interact with many of the same molecules usually implicated in the action of psychotropic drugs. The importance of such events cannot be overstated, as the misdiagnosis of an adverse drug reaction as a symptom of a primary psychiatric or neurological disorder entails great suffering for the patient affected as well as significant costs for the healthcare system...
February 14, 2017: Clinical Drug Investigation
https://www.readbyqxmd.com/read/28196887/spontaneous-activity-in-the-piriform-cortex-extends-the-dynamic-range-of-cortical-odor-coding
#20
Malinda L S Tantirigama, Helena H-Y Huang, John M Bekkers
Neurons in the neocortex exhibit spontaneous spiking activity in the absence of external stimuli, but the origin and functions of this activity remain uncertain. Here, we show that spontaneous spiking is also prominent in a sensory paleocortex, the primary olfactory (piriform) cortex of mice. In the absence of applied odors, piriform neurons exhibit spontaneous firing at mean rates that vary systematically among neuronal classes. This activity requires the participation of NMDA receptors and is entirely driven by bottom-up spontaneous input from the olfactory bulb...
February 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
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