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GABA receptors

Chenshuang Li, Zhong Zheng, Pin Ha, Xiaoyan Chen, Wenlu Jiang, Shan Sun, Feng Chen, Greg Asatrian, Emily A Berthiaume, Jong Kil Kim, Eric C Chen, Shen Pang, Xinli Zhang, Kang Ting, Chia Soo
Contactin-associated protein-like 4 (Cntnap4) is a member of the neurexin superfamily of transmembrane molecules that have critical functions in neuronal cell communication. Cntnap4 knockout mice display decreased presynaptic gamma-aminobutyric acid (GABA) and increased dopamine release that is associated with severe, highly penetrant, repetitive, and perseverative movements commonly found in human autism spectrum disorder patients. However, no known function of Cntnap4 has been revealed besides the nervous system...
June 15, 2018: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
Saraí Trujeque-Ramos, Diego Castillo-Rolón, Elvira Galarraga, Dagoberto Tapia, Gabina Arenas-López, Stefan Mihailescu, Salvador Hernández-López
Recent studies, have shown that insulin increases extrasynaptic GABAA receptor-mediated currents in the hippocampus, causing alterations of neuronal excitability. The prefrontal cortex (PFC) is another brain area which is involved in cognition functions and expresses insulin receptors. Here, we used electrophysiological, molecular, and immunocytochemical techniques to examine the effect of insulin on the extrasynaptic GABAA receptor-mediated tonic currents in brain slices. We found that insulin (20-500 nM) increases GABAA -mediated tonic currents...
2018: Frontiers in Neuroscience
Martin W Nicholson, Aaron Sweeney, Eva Pekle, Sabina Alam, Afia B Ali, Michael Duchen, Jasmina N Jovanovic
Benzodiazepines facilitate the inhibitory actions of GABA by binding to γ-aminobutyric acid type A receptors (GABAA Rs), GABA-gated chloride/bicarbonate channels, which are the key mediators of transmission at inhibitory synapses in the brain. This activity underpins potent anxiolytic, anticonvulsant and hypnotic effects of benzodiazepines in patients. However, extended benzodiazepine treatments lead to development of tolerance, a process which, despite its important therapeutic implications, remains poorly characterised...
June 14, 2018: Molecular Psychiatry
Elif Engin, Rebecca S Benham, Uwe Rudolph
In the past 20 years we have learned a great deal about GABAA receptor (GABAA R) subtypes, and which behaviors are regulated or which drug effects are mediated by each subtype. However, the question of where GABAA Rs involved in specific drug effects and behaviors are located in the brain remains largely unanswered. We review here recent studies taking a circuit pharmacology approach to investigate the functions of GABAA R subtypes in specific brain circuits controlling fear, anxiety, learning, memory, reward, addiction, and stress-related behaviors...
May 25, 2018: Trends in Pharmacological Sciences
Dongsheng Xu, Hui Zhao, Han Gao, Huling Zhao, Dandan Liu, Jing Li
BACKGROUND: Neuropathic pain is observed in patients as chemotherapeutic oxaliplatin (OXL) is used to treat metastatic digestive tumors; however, the mechanisms responsible for hyperalgesia are not well understood. Chronic neuroinflammation is one of the hallmarks of pathophysiology of neuropathic pain. Since the midbrain periaqueductal gray (PAG) is an important component of the descending inhibitory pathway controlling on central pain transmission, we examined the role for pro-inflammatory cytokines (PICs) system of the PAG in regulating mechanical hyperalgesia and cold hypersensitivity evoked by OXL...
January 1, 2018: Molecular Pain
Richard Piet, Bruna Kalil, Tim McLennan, Robert Porteous, Katja Czieselsky, Allan E Herbison
A population of kisspeptin-GABA co-expressing neurons located in the rostral periventricular area of the third ventricle (RP3V) is believed to activate gonadotropin-releasing hormone (GnRH) neurons to generate the luteinizing hormone (LH) surge triggering ovulation. Selective optogenetic activation of RP3V kisspeptin (RP3VKISS ) neurons in female mice for >30s and ≥10Hz in either a continuous or bursting mode was found to reliably generate a delayed and long-lasting activation of GnRH neuron firing in brain slices...
June 13, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Xin Zhang, Tong Tong Ge, Guanghao Yin, Ranji Cui, Guoqing Zhao, Wei Yang
The amygdala plays a major role in the processing of physiologic and behavioral responses to stress and is characterized by gamma-aminobutyric acid (GABA)-mediated high inhibitory tone under resting state. Human and animal studies showed that stress lead to a hyperactivity of amygdala, which was accompanied by the removal of inhibitory control. However, the contribution of hyperactivity of amygdala to stress-induced neuropsychiatric diseases, such as anxiety and mood disorders, is still dubious. In this review, we will summarize stress-induced various structural and functional alterations in amygdala, including the GABA receptors expression, GABAergic transmission and synaptic plasticity...
2018: Frontiers in Neuroscience
Tian Zhang, Jun Li, Hao Yu, Yongyong Shi, Zhiqiang Li, Linyan Wang, Ziqi Wang, Tianlan Lu, Lifang Wang, Weihua Yue, Dai Zhang
Schizophrenia (SCZ) is a severe psychiatric disorder with evidence of a strong genetic component in the complex etiologies. Some studies indicated that gamma-aminobutyric acid (GABA)A receptor β2 subunit gene (GABRB2) was associated with SCZ. Other studies reported a negative association. Moreover, the results of two previous meta-analyses of GABRB2 with SCZ were inconsistent and the sample sizes were limited. Therefore, an updated meta-analysis combined with genome-wide association study (GWAS) data of the Han Chinese population and Psychiatric Genomics Consortium (PGC) was performed...
2018: PloS One
Bojan Batinić, Tamara Stanković, Michael Rajesh Stephen, Revathi Kodali, Veera V Tiruveedhula, Guanguan Li, Petra Scholze, Bojan D Marković, Aleksandar Lj Obradović, Margot Ernst, James M Cook, Miroslav M Savić
It is unclear whether GABAA receptors (GABAA Rs) that contain the α3-subunit are substantially involved in the anxiolytic effects of benzodiazepines (BDZs). In the present study, we tested YT-III-31, a newer BDZ ligand with functional preference for α3βγ2 GABAA Rs, in two paradigms of unconditioned anxiety, the open field and elevated plus maze in rats. The effective dose of YT-III-31 (2 mg/kg) displayed a clear anxiolytic-like profile, unhampered by sedative action, in both tests. At a higher dose (10 mg/kg), YT-III-31 induced ataxia in the rotarod and sedation in spontaneous locomotor activity test...
June 8, 2018: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
Kathryn A Jewett, Kwan Young Lee, Daphne E Eagleman, Stephanie Soriano, Nien-Pei Tsai
Chronic activity perturbations in neurons induce homeostatic plasticity through modulation of synaptic strength or other intrinsic properties to maintain the correct physiological range of excitability. Although similar plasticity can also occur at the population level, what molecular mechanisms are involved remain unclear. In the current study, we utilized a multielectrode array (MEA) recording system to evaluate homeostatic neural network activity of primary mouse cortical neuron cultures. We demonstrated that chronic elevation of neuronal activity through the inhibition of GABA(A) receptors elicits synchronization of neural network activity and homeostatic reduction of the amplitude of spontaneous neural network spikes...
June 8, 2018: Neuropharmacology
Shiwei Song, Abul Fajol, Yan Chen, Baogang Ren, Songsheng Shi
Epilepsy is associated with increased morbidity and mortality together and places a large financial burden on individuals and society. To evaluate the anticonvulsant action of protodioscin (PDSN) in experiments with animals with pilocarpine-induced convulsions. We assessed the activity of PDSN in pilocarpine induced seizures in combination with different agents which are acting via diverse receptors, such as atropine, memantine, nimodipine, diazepam, and flumazenil, to determine the exact receptors responsible for the action of PDSN...
June 7, 2018: European Journal of Pharmacology
Julia V Bukanova, Elena I Solntseva, Sergey N Kolbaev, Eva Kudova
The ability of pregnanolone glutamate (PA-Glu), pregnanolone hemisuccinate (PA-hSuc) and pregnanolone hemipimelate (PA-hPim), neuroactive steroids with a negative modulatory effect on excitatory N-methyl-d-aspartate receptors, to influence the functional activity of inhibitory γ-aminobutyric acid and glycine receptors was estimated. The GABA- and glycine-induced chloride currents (IGABA and IGly ) were measured in isolated pyramidal neurons of the rat hippocampus using the patch-clamp technique. Compound PA-Glu was found to potentiate IGABA and to inhibit IGly , while PA-hSuc and PA-hPim inhibited both IGABA and IGly ...
June 7, 2018: Neurochemistry International
Chelsie L Brewer, Mark L Baccei
Clinical and basic science research have revealed persistent effects of early life injury on nociceptive processing and resulting pain sensitivity. While recent work has identified clear deficits in fast GABAA - and glycine receptor-mediated inhibition in the adult spinal dorsal horn after neonatal tissue damage, the effects of early injury on slow, metabotropic inhibition within spinal pain circuits are poorly understood. Here we provide evidence that neonatal surgical incision significantly enhances postsynaptic GABAB receptor signaling within the mature superficial dorsal horn (SDH) in a cell type-dependent manner...
June 6, 2018: Neuroscience
Danica Bajic, Krisztina Monory, Andrea Conrad, Christina Maul, Roland M Schmid, Carsten T Wotjak, Christoph K Stein-Thoeringer
Endocannabinoids acting through cannabinoid receptor type 1 (CB1) are major modulators of peripheral somatic and visceral nociception. Although only partially studied, some evidence suggests a particular role of CB1 within the brain in nociceptive processes. As the endocannabinoid system regulates affect and emotional behaviors, we hypothesized that cerebral CB1 influences affective processing of visceral pain-related behaviors in laboratory animals. To study nocifensive responses modulated by supraspinal CB1, we used conditional knock-out mice lacking CB1 either in cortical glutamatergic neurons (Glu-CB1-KO), or in forebrain GABAergic neurons (GABA-CB1-KO), or in principle neurons of the forebrain (CaMK-CB1-KO)...
June 6, 2018: Neuroscience
Yanbo Jiang, Yujie Xiao, Xiaoxue Zhang, Yousheng Shu
Ionotropic GABAA receptors expressing at the axon initial segment (AIS) of glutamatergic pyramidal cell (PC) in the cortex plays critical roles in regulating action potential generation. However, it remains unclear whether these receptors also express at the AIS of cortical GABAergic interneurons. In mouse prefrontal cortical slices, we performed experiments at the soma and AIS of the two most abundant GABAergic interneurons: parvalbumin (PV) and somatostatin (SST) positive neurons. Local application of GABA at the perisomatic axonal regions could evoke picrotoxin-sensitive currents with a reversal potential near the Cl- equilibrium potential...
May 23, 2018: Neuropharmacology
Semen V Nesterov, Yulia A Skorobogatova, Alisa A Panteleeva, Lyubov L Pavlik, Irina B Mikheeva, Lev S Yaguzhinsky, Yaroslav R Nartsissov
The purpose of this study is to demonstrate the presence of three more receptors in mitochondria. Two N-methyl-d-aspartate receptor (NMDAR) subunits (NR1 and NR2B) are found by protein immunoblot and immunogold labeling in mitochondria fraction isolated from rat heart. These data allow supposing NMDAR presence and functioning in the inner mitochondrial membrane. There are no signs of receptor presence obtained in heart tissue lysate, that indicates the receptor localization exactly in mitochondria. The possible receptor functions discussed are its participation in calcium transport and in excitation-metabolism coupling...
June 5, 2018: Chemico-biological Interactions
Khaled Zemoura, Karthik Balakrishnan, Thomas Grampp, Dietmar Benke
The G protein-coupled GABAB receptors, constituted from GABAB1 and GABAB2 subunits, are important regulators of neuronal excitability by mediating long-lasting inhibition. One factor that determines receptor availability and thereby the strength of inhibition is regulated protein degradation. GABAB receptors are constitutively internalized from the plasma membrane and are either recycled to the cell surface or degraded in lysosomes. Lys-63-linked ubiquitination mediated by the E3 ligase Mind bomb-2 (MIB2) is the signal that sorts GABAB receptors to lysosomes...
June 7, 2018: Molecular Neurobiology
Alexandra Pallottie, Ayomi Ratnayake, Li Ni, Cigdem Acioglu, Lun Li, Ersilia Mirabelli, Robert F Heary, Stella Elkabes
Spinal cord (SC) trauma elicits pathological changes at the primary lesion and in regions distant from the injury epicenter. Therapeutic agents that target mechanisms at the injury site are likely to exert additional effects in these remote regions. We previously reported that a toll-like receptor 9 (TLR9) antagonist, oligodeoxynucleotide 2088 (ODN 2088), improves functional deficits and modulates the milieu at the epicenter in mice sustaining a mid-thoracic contusion. The present investigations use the same paradigm to assess ODN 2088-elicited alterations in the lumbar dorsal horn (LDH), a region remote from the injury site where SCI-induced molecular alterations have been well defined...
June 7, 2018: Scientific Reports
Juan Pablo Del Río, María I Alliende, Natalia Molina, Felipe G Serrano, Santiago Molina, Pilar Vigil
Sex hormones significantly impact women's lives. Throughout the different stages of life, from menarche to menopause and all stages in between, women experience dramatic fluctuations in the levels of progesterone and estradiol, among other hormones. These fluctuations affect the body as a whole, including the central nervous system (CNS). In the CNS, sex hormones act via steroid receptors. They also have an effect on different neurotransmitters such as GABA, serotonin, dopamine, and glutamate. Additionally, studies show that sex hormones and their metabolites influence brain areas that regulate mood, behavior, and cognitive abilities...
2018: Frontiers in Public Health
Ken T Wakabayashi, Malte Feja, Ajay N Baindur, Michael J Bruno, Rohan V Bhimani, Jinwoo Park, Kathryn Hausknecht, Roh-Yu Shen, Samir Haj-Dahmane, Caroline E Bass
Cues predicting rewards can gain motivational properties and initiate reward-seeking behaviors. Dopamine projections from the ventral tegmental area (VTA) to the nucleus accumbens (NAc) are critical in regulating cue-motivated responding. Although, approximately one third of mesoaccumbal projection neurons are GABAergic, it is unclear how this population influences motivational processes and cue processing. This is largely due to our inability to pharmacologically probe circuit level contributions of VTA-GABA, which arises from diverse sources, including multiple GABA afferents, interneurons, and projection neurons...
May 22, 2018: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
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