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https://www.readbyqxmd.com/read/28547758/ghrelin-receptors-mediate-ghrelin-induced-excitation-of-agrp-npy-but-not-pomc-neurons
#1
Shao-Rui Chen, Hong Chen, Jing-Jing Zhou, Geetali Pradhan, Yuxiang Sun, Hui-Lin Pan, De-Pei Li
Ghrelin increases food intake and body weight by stimulating orexigenic AgRP/NPY neurons and inhibiting anoexic POMC neurons in the hypothalamus. Growth hormone secretagogue receptor (Ghsr) mediates the effect of ghrelin on feeding behavior and energy homeostasis. However, the role of Ghsr in the ghrelin effect on these two populations of neurons is unclear. We hypothesized that Ghsr mediates the effect of ghrelin on AgRP and POMC neurons. In this study, we determined whether Ghsr similarly mediates the effects of ghrelin on AgRP/NPY and POMC neurons using cell type-specific Ghsr-knockout mice...
May 26, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28547292/physiological-implications-of-ocean-acidification-for-marine-fish-emerging-patterns-and-new-insights
#2
REVIEW
Andrew J Esbaugh
Ocean acidification (OA) is an impending environmental stress facing all marine life, and as such has been a topic of intense research interest in recent years. Numerous detrimental effects have been documented in marine fish, ranging from reduced mortality to neurosensory impairment, and the prevailing opinions state that these effects are largely the downstream consequences of altered blood carbon dioxide chemistry caused by respiratory acid-base disturbances. While the respiratory acid-base disturbances are consistent responses to OA across tested fish species, it is becoming increasingly clear that there is wide variability in the degree of downstream impairments between species...
May 25, 2017: Journal of Comparative Physiology. B, Biochemical, Systemic, and Environmental Physiology
https://www.readbyqxmd.com/read/28546770/reduced-gabaergic-neuronal-activity-in-zona-incerta-causes-neuropathic-pain-in-a-rat-sciatic-nerve-chronic-constriction-injury-model
#3
Hyeong Cheol Moon, Young Seok Park
PURPOSE: The zona incerta (ZI) is below the ventral tier of the thalamus and has a strong influence selectively in higher-order thalamic relays. Although neuropathic pain has been suggested to result from reduced gamma-aminobutyric acid (GABA) and GABAergic signaling in the ZI, the mechanisms remain unclear. Here, the role of GABA and GABAergic signaling was investigated in the ZI in neuropathic pain using sciatic nerve chronic constriction injury (CCI) rats. MATERIALS AND METHODS: Single-unit neuronal activity was recorded, and microdialysis was performed in the ZI of CCI rats and sham-treated rats in vivo...
2017: Journal of Pain Research
https://www.readbyqxmd.com/read/28544625/a-mutation-in-gabrb3-associated-with-dravet-syndrome
#4
Sy Vinh Le, Phan Hoang Truc Le, Thi Khanh Van Le, Thi Thuy Kieu Huynh, Thi Thu Hang Do
Dravet syndrome is a rare and severe type of epilepsy in infants. Approximately, 70-80% of patients with Dravet syndrome have mutations in SCN1A, the gene encoding the alpha-1 subunit of the sodium channel, while some simplex patients have variants in one of several other genes, including but not limited to GABRA1, SCN2A, STXBP1, GABRG2, and SCN1B. In this study, we performed exome sequencing in six patients with SCN1A-negative Dravet syndrome to identify other genes related to this disorder. In one affected individual, we detected a novel de novo heterozygous missense variant, c...
May 24, 2017: American Journal of Medical Genetics. Part A
https://www.readbyqxmd.com/read/28536106/alpha-2-subunit-containing-gabaa-receptor-subtypes-are-up-regulated-and-contribute-to-alcohol-induced-functional-plasticity-in-rat-hippocampus
#5
A Kerstin Lindemeyer, Yi Shen, Ferin Yazdani, Xuesi M Shao, Igor Spigelman, Daryl L Davies, Richard W Olsen, Jing Liang
Alcohol(EtOH)intoxication causes changes in rodent brain GABAA receptor (GABAAR) subunit composition and function, playing a crucial role in EtOH withdrawal symptoms and dependence. Building evidence indicates withdrawal from acute EtOH and chronic intermittent EtOH (CIE) results in decreased EtOH-enhanced GABAAR δ subunit-containing extrasynaptic and EtOH-insensitive α1βγ2 subtype synaptic GABAARs, but increased synaptic α4βγ2 subtype, and increased EtOH sensitivity of GABAAR miniature postsynaptic currents (mIPSCs) correlated with EtOH dependence...
May 23, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28535436/microcystin-lr-induces-changes-in-the-gaba-neurotransmitter-system-of-zebrafish
#6
Wei Yan, Li Li, Guangyu Li, Sujuan Zhao
It has been reported that exposure to microcystins altered adult zebrafish swimming performance parameters, but the possible mechanisms of action remain unknown. Neuronal activity depends on the balance between the number of excitatory and inhibitory processes which are associated with neurotransmitters. In the present study, zebrafish embryos (5 d post-fertilization) were exposed to 0, 0.3, 3 and 30μg/L (microcystin-LR) MCLR for 90day until reaching sexual maturity. To investigate the effects of MCLR on the neurotransmitter system, mRNA levels involved in amino acid g-aminobutyric acid (GABA) and glutamate metabolic pathways were tested using quantitative real-time PCR...
May 15, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28529315/disinhibition-of-somatostatin-positive-interneurons-by-deletion-of-postsynaptic-gabaa-receptors
#7
T Fuchs, S J Jefferson, A Hooper, P-H P Yee, J Maguire, B Luscher
No abstract text is available yet for this article.
June 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28529139/psychopharmacology-of-combined-activation-of-the-serotonin1a-and-%C3%AF-1-receptors
#8
REVIEW
Yukio Ago, Shigeru Hasebe, Naoki Hiramatsu, Hitoshi Hashimoto, Kazuhiro Takuma, Toshio Matsuda
The selective serotonin (5-HT) reuptake inhibitors (SSRIs) are generally used for the treatment of major depressive disorders, and the 5-HT1A and σ1 receptors are considered to be targets for treatment of psychiatric disorders. Some SSRIs such as fluvoxamine have agonistic activity towards for the σ1 receptor, but it is not known whether the effect on the receptor plays a key role in the pharmacological effects. We have recently demonstrated that fluvoxamine shows an anti-anhedonic effect in picrotoxin-induced model of anxiety/depression, while the SSRI paroxetine, which have little affinity for the σ1 receptor, does not...
May 18, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28528665/gabaa-receptors-and-the-diversity-in-their-structure-and-pharmacology
#9
Han Chow Chua, Mary Chebib
GABAA receptors (GABAARs) are a class of ligand-gated ion channels with high physiological and therapeutic significance. In the brain, these pentameric receptors occur with diverse subunit composition, which confers highly complex pharmacology to this receptor class. An impressive range of clinically used therapeutics are known to bind to distinct sites found on GABAARs to modulate receptor function. Numerous experimental approaches have been used over the years to elucidate the binding sites of these drugs, but unequivocal identification is challenging due to subtype- and ligand-dependent pharmacology...
2017: Advances in Pharmacology
https://www.readbyqxmd.com/read/28528187/anticonvulsant-activity-of-pseudospondias-microcarpa-a-rich-engl-hydroethanolic-leaf-extract-in-mice-the-role-of-excitatory-inhibitory-neurotransmission-and-nitric-oxide-pathway
#10
Donatus W Adongo, Priscilla K Mante, Kennedy K E Kukuia, Robert P Biney, Eric Boakye-Gyasi, Charles K Benneh, Elvis O Ameyaw, Eric Woode
ETHNOPHARMACOLOGICAL RELEVANCE: Pseudospondias microcarpa (A. Rich) Engl. is a plant used for managing various diseases including central nervous system disorders. AIM OF THE STUDY: This study explored the anticonvulsant activity of P. microcarpa hydroethanolic leaf extract (PME) as well as possible mechanism(s) of action in animal models. METHODS: Effects of PME was assessed in electroconvulsive (the maximal electroshock and 6-Hz seizures) and chemoconvulsive (pentylenetetrazole-, picrotoxin-, isoniazid-, 4-aminopyridine-, and strychnine-induced seizures) models of epilepsy...
May 17, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28521115/anticonvulsant-profile-of-the-neuroactive-steroid-sge-516-in-animal-models
#11
Rebecca S Hammond, Alison L Althaus, Michael A Ackley, Carla Maciag, Gabriel Martinez Botella, Francesco G Salituro, Albert J Robichaud, James J Doherty
Despite the availability of multiple antiepileptic drugs (AED), failure to adequately control seizures is a challenge for approximately one third of epilepsy patients, and new therapies with a differentiated mechanism of action are needed. The neuroactive steroid, SGE-516, is a positive allosteric modulator of both gamma- and delta-containing GABAA receptors. This broad GABAA receptor activity differentiates neuroactive steroids like SGE-516 from benzodiazepines, a class of anticonvulsants which have been shown in vitro to selectively target gamma-subunit containing GABAA receptors...
May 7, 2017: Epilepsy Research
https://www.readbyqxmd.com/read/28514655/inhibitory-control-of-feature-selectivity-in-an-object-motion-sensitive-circuit-of-the-retina
#12
Tahnbee Kim, Daniel Kerschensteiner
Object motion sensitive (OMS) W3-retinal ganglion cells (W3-RGCs) in mice respond to local movements in a visual scene but remain silent during self-generated global image motion. The excitatory inputs that drive responses of W3-RGCs to local motion were recently characterized, but which inhibitory neurons suppress W3-RGCs' responses to global motion, how these neurons encode motion information, and how their connections are organized along the excitatory circuit axis remains unknown. Here, we find that a genetically identified amacrine cell (AC) type, TH2-AC, exhibits fast responses to global motion and slow responses to local motion...
May 16, 2017: Cell Reports
https://www.readbyqxmd.com/read/28511229/hplc-based-activity-profiling-for-gabaa-receptor-modulators-in-searsia-pyroides-using-a-larval-zebrafish-locomotor-assay
#13
Fahimeh Moradi-Afrapoli, Hannes van der Merwe, Maria De Mieri, Anke Wilhelm, Marco Stadler, Pieter C Zietsman, Steffen Hering, Kenneth Swart, Matthias Hamburger
A dichloromethane extract from leaves of Searsia pyroides potentiated gamma aminobutyric acid-induced chloride currents by 171.8 ± 54% when tested at 100 µg/mL in Xenopus oocytes transiently expressing gamma aminobutyric acid type A receptors composed of α1β2γ2s subunits. In zebrafish larvae, the extract significantly lowered pentylenetetrazol-provoked locomotion when tested at 4 µg/mL. Active compounds of the extract were tracked with the aid of HPLC-based activity profiling utilizing a previously validated zebrafish larval locomotor activity assay...
May 16, 2017: Planta Medica
https://www.readbyqxmd.com/read/28505538/synthesis-and-pharmacological-evaluation-of-neurosteroid-photoaffinity-ligands
#14
Pavel Y Savechenkov, David C Chiara, Rooma Desai, Alexander T Stern, Xiaojuan Zhou, Alexis M Ziemba, Andrea L Szabo, Yinghui Zhang, Jonathan B Cohen, Stuart A Forman, Keith W Miller, Karol S Bruzik
Neuroactive steroids are potent positive allosteric modulators of GABAA receptors (GABAAR), but the locations of their GABAAR binding sites remain poorly defined. To discover these sites, we synthesized two photoreactive analogs of alphaxalone, an anesthetic neurosteroid targeting GABAAR, 11β-(4-azido-2,3,5,6-tetrafluorobenzoyloxy)allopregnanolone, (F4N3Bzoxy-AP) and 11-aziallopregnanolone (11-AziAP). Both photoprobes acted with equal or higher potency than alphaxalone as general anesthetics and potentiators of GABAAR responses, left-shifting the GABA concentration - response curve for human α1β3γ2 GABAARs expressed in Xenopus oocytes, and enhancing [(3)H]muscimol binding to α1β3γ2 GABAARs expressed in HEK293 cells...
April 21, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28496108/alpha7-nicotinic-acetylcholine-receptor-agonist-promotes-retinal-ganglion-cell-function-via-modulating-gabaergic-presynaptic-activity-in-a-chronic-glaucomatous-model
#15
Xujiao Zhou, Yun Cheng, Rong Zhang, Gang Li, Boqi Yang, Shenghai Zhang, Jihong Wu
Alpha-7 nicotinic acetylcholine receptor (α7-nAChR) agonists can prevent glutamate-induced excitotoxicity in cultured retinal ganglion cells (RGCs). However, the neuroprotective effects and the mechanism of action of PNU-282987, an α7-nAChR agonist, in a chronic in vivo rat glaucoma model are poorly understood. We found that elevated intraocular pressure (IOP) downregulated retinal α7-nAChR expression. Electroretinography revealed that the amplitude of the photopic negative response (PhNR) decreased in parallel with the loss of RGCs caused by elevated IOP...
May 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28495376/gabaa-receptor-positive-allosteric-modulators-modify-the-abuse-related-behavioral-and-neurochemical-effects-of-methamphetamine-in-rhesus-monkeys
#16
Laís F Berro, Monica L Andersen, Sergio Tufik, Leonard L Howell
GABAA receptor positive allosteric modulators (GABAA receptor modulators) are commonly used for the treatment of insomnia. Nevertheless, the effects of these compounds on psychostimulant-induced sleep impairment are poorly understood. Because GABAA receptor modulators have been shown to decrease the abuse-related effects of psychostimulants, the aim of the present study was to evaluate the effects of temazepam (0.3, 1.0 or 3.0 mg/kg) and eszopiclone (0.3, 1.0 or 3.0 mg/kg), two GABAA receptor modulators, on the behavioral neuropharmacology of methamphetamine in adult rhesus macaques (n = 5)...
May 8, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28491031/control-of-absence-seizures-by-the-thalamic-feed-forward-inhibition
#17
Mingming Chen, Daqing Guo, Yang Xia, Dezhong Yao
As a subtype of idiopathic generalized epilepsies, absence epilepsy is believed to be caused by pathological interactions within the corticothalamic (CT) system. Using a biophysical mean-field model of the CT system, we demonstrate here that the feed-forward inhibition (FFI) in thalamus, i.e., the pathway from the cerebral cortex (Ctx) to the thalamic reticular nucleus (TRN) and then to the specific relay nuclei (SRN) of thalamus that are also directly driven by the Ctx, may participate in controlling absence seizures...
2017: Frontiers in Computational Neuroscience
https://www.readbyqxmd.com/read/28485933/hplc-based-activity-profiling-for-gabaa-receptor-modulators-in-extracts-validation-of-an-approach-utilizing-a-larval-zebrafish-locomotor-assay
#18
Fahimeh Moradi-Afrapoli, Samad Nejad Ebrahimi, Martin Smiesko, Matthias Hamburger
Gamma-aminobutyric acid type A (GABAA) receptors are major inhibitory neurotransmitter receptors in the central nervous system and a target for numerous clinically important drugs used to treat anxiety, insomnia, and epilepsy. A series of allosteric GABAA receptor agonists was identified previously with the aid of HPLC-based activity profiling, whereby activity was tracked with an electrophysiological assay in Xenopus laevis oocytes. To accelerate the discovery process, an approach has been established for HPLC-based profiling using a larval zebrafish (Danio rerio) seizure model induced by pentylenetetrazol (PTZ), a pro-convulsant GABAA receptor antagonist...
May 9, 2017: Journal of Natural Products
https://www.readbyqxmd.com/read/28484025/common-general-anesthetic-propofol-impairs-kinesin-processivity
#19
Brandon M Bensel, Stephanie Guzik-Lendrum, Erin M Masucci, Kellie A Woll, Roderic G Eckenhoff, Susan P Gilbert
Propofol is the most widely used i.v. general anesthetic to induce and maintain anesthesia. It is now recognized that this small molecule influences ligand-gated channels, including the GABAA receptor and others. Specific propofol binding sites have been mapped using photoaffinity ligands and mutagenesis; however, their precise target interaction profiles fail to provide complete mechanistic underpinnings for the anesthetic state. These results suggest that propofol and other common anesthetics, such as etomidate and ketamine, may target additional protein networks of the CNS to contribute to the desired and undesired anesthesia end points...
May 23, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28483674/the-postnatal-5-ht1a-receptor-regulates-adult-anxiety-and-depression-differently-via-multiple-molecules
#20
Chihiro Ishikawa, Takashi Shiga
Serotonin (5-HT) and the 5-HT1A receptor during development are known to modulate anxiety and depression in later life. However, the brain mechanisms linking the postnatal 5-HT system and adult behavior remain unknown. Here, we examined the effects of pharmacological 5-HT1A receptor activation during the postnatal period on anxiety and depression-like behavior in adult BALB/c male mice. To elucidate the underlying mechanisms, we measured mRNA expression of the 5-HT1A receptor, brain-derived neurotrophic factor (BDNF), GABAA receptor subunits, and AMPA receptor subunits in the medial prefrontal cortex (mPFC), amygdala, and hippocampus...
May 5, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
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