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https://www.readbyqxmd.com/read/28323246/the-role-of-spinal-gabab-receptors-in-cancelr-induced-bone-pain-in-rats
#1
Ya-Qun Zhou, Shu-Ping Chen, Dai-Qiang Liu, Anne Manyande, Wen Zhang, Shao-Bing Yang, Bing-Rui Xiong, Qiao-Chu Fu, Zhen-Peng Song, Heike Rittner, Da-Wei Ye, Yu-Ke Tian
Cancer-induced bone pain (CIBP) remains a major challenge in advanced cancer patients due to our lack of understanding of its mechanisms. Previous studies have demonstrated the vital role of GABAB receptors (GABABRs) in regulating nociception and various neuropathic pain models have shown diminished activity of GABABRs. However, the role of spinal GABABRs in CIBP remains largely unknown. In this study, we investigated the specific cellular mechanisms of GABABRs in the development and maintenance of CIBP in rats...
March 18, 2017: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/28299422/homeostatic-regulation-through-gaba-and-acetylcholine-muscarinic-receptors-of-motor-trigeminal-neurons-following-sleep-deprivation
#2
Hanieh Toossi, Esther Del Cid-Pellitero, Barbara E Jones
Muscle tone is regulated across sleep-wake states, being maximal in waking, reduced in slow wave sleep (SWS) and absent in paradoxical or REM sleep (PS or REMS). Such changes in tone have been recorded in the masseter muscles and shown to correspond to changes in activity and polarization of the trigeminal motor 5 (Mo5) neurons. The muscle hypotonia and atonia during sleep depend in part on GABA acting upon both GABAA and GABAB receptors (Rs) and acetylcholine (ACh) acting upon muscarinic 2 (AChM2) Rs. Here, we examined whether Mo5 neurons undergo homeostatic regulation through changes in these inhibitory receptors following prolonged activity with enforced waking...
March 15, 2017: Brain Structure & Function
https://www.readbyqxmd.com/read/28272206/limbic-encephalitis-associated-with-anti-nh2-terminal-of-%C3%AE-enolase-antibodies-a-clinical-subtype-of-hashimoto-encephalopathy
#3
Toru Kishitani, Akiko Matsunaga, Masamichi Ikawa, Kouji Hayashi, Osamu Yamamura, Tadanori Hamano, Osamu Watanabe, Keiko Tanaka, Yasunari Nakamoto, Makoto Yoneda
Several types of autoantibodies have been reported in autoimmune limbic encephalitis (LE), such as antibodies against the voltage-gated potassium channel (VGKC) complex including leucine-rich glioma inactivated 1 (LGI1). We recently reported a patient with autoimmune LE and serum anti-NH2-terminal of α-enolase (NAE) antibodies, a specific diagnostic marker for Hashimoto encephalopathy (HE), who was diagnosed with HE based on the presence of antithyroid antibodies and responsiveness to immunotherapy. This case suggests that LE patients with antibodies to both the thyroid and NAE could be diagnosed with HE and respond to immunotherapy...
March 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28262662/epilepsy-and-intellectual-disability-linked-protein-shrm4-interaction-with-gababrs-shapes-inhibitory-neurotransmission
#4
Jonathan Zapata, Edoardo Moretto, Saad Hannan, Luca Murru, Anna Longatti, Davide Mazza, Lorena Benedetti, Matteo Fossati, Christopher Heise, Luisa Ponzoni, Pamela Valnegri, Daniela Braida, Mariaelvina Sala, Maura Francolini, Jeffrey Hildebrand, Vera Kalscheuer, Francesca Fanelli, Carlo Sala, Bernhard Bettler, Silvia Bassani, Trevor G Smart, Maria Passafaro
Shrm4, a protein expressed only in polarized tissues, is encoded by the KIAA1202 gene, whose mutations have been linked to epilepsy and intellectual disability. However, a physiological role for Shrm4 in the brain is yet to be established. Here, we report that Shrm4 is localized to synapses where it regulates dendritic spine morphology and interacts with the C terminus of GABAB receptors (GABABRs) to control their cell surface expression and intracellular trafficking via a dynein-dependent mechanism. Knockdown of Shrm4 in rat severely impairs GABABR activity causing increased anxiety-like behaviour and susceptibility to seizures...
March 6, 2017: Nature Communications
https://www.readbyqxmd.com/read/28213518/deficits-in-the-activity-of-presynaptic-%C3%AE-aminobutyric-acid-type-b-receptors-contribute-to-altered-neuronal-excitability-in-fragile-x-syndrome
#5
Ji-Yong Kang, Jayashree Chadchankar, Thuy N Vien, Michelle I Mighdoll, Thomas M Hyde, Robert J Mather, Tarek Z Deeb, Menelas N Pangalos, Nicholas J Brandon, John Dunlop, Stephen J Moss
The behavioral and anatomical deficits seen in Fragile X syndrome (FXS) are widely believed to result from imbalances in the relative strengths of excitatory and inhibitory neurotransmission. While modified neuronal excitability is thought to be of significance, the contribution that alterations in GABAergic inhibition play in the pathophysiology of FXS are ill-defined. Slow sustained neuronal inhibition is mediated by γ-aminobutyric acid type B (GABAB) receptors, which are heterodimeric G-protein coupled receptors constructed from R1a and R2 or R1b and R2 subunits...
February 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28104407/metabotropic-glutamate-and-gaba-receptors-modulate-cellular-excitability-and-glutamatergic-transmission-in-chicken-cochlear-nucleus-angularis-neurons
#6
Wei Shi, Yong Lu
Neurons in the avian cochlear nucleus angularis (NA) receive glutamatergic input from the auditory nerve, and GABAergic input from the superior olivary nucleus. Physiologically heterogeneous, NA neurons perform multiple functions including encoding sound intensity information. Using in vitro whole-cell patch recordings from acute brain slices and immunohistochemistry staining, we investigated neuromodulation mediated by metabotropic glutamate and GABA receptors (mGluRs and GABABRs) in NA neurons. Based on their intrinsic firing patterns in response to somatic current injections, NA neurons were classified into onset, damped, and tonic cells...
March 2017: Hearing Research
https://www.readbyqxmd.com/read/28081431/clinical-characterization-of-autoimmune-encephalitis-and-psychosis
#7
Qinjian Hao, Dahai Wang, Lanting Guo, Bo Zhang
BACKGROUND AND PURPOSE: Autoimmune disorders are growing alarmingly high in prevalence across the globe. Autoimmune encephalitis has had a dramatic impact on the medical field, effectually altering diagnostic and treatment paradigms in regard to neuropsychiatric disorders. Our primary goal in conducting this study was to analyze the clinical characteristics of autoimmune encephalitis patients, with special focus on psychiatric presentations, in the West China Hospital and report patient prognoses after immunotherapy...
December 27, 2016: Comprehensive Psychiatry
https://www.readbyqxmd.com/read/27979827/protective-roles-of-hepatic-gaba-signaling-in-acute-liver-injury-of-rats
#8
Shuanglian Wang, Yun-Yan Xiang, Jianchun Zhu, Fan Yi, Jingxin Li, Chuanyong Liu, Wei-Yang Lu
Gamma-aminobutyric acid (GABA) is produced by various cells through the catalytic activity of glutamic acid decarboxylase (GAD). Activation of type-A GABA receptor (GABAAR) inhibits stem cell proliferation but protects differentiated cells from injures. The present study investigated hepatic GABA signaling system and the role of this system in liver physiology and pathophysiology. RT-PCR and immunoblot assays identified GAD and GABAAR subunits in rat livers and in HepG2 and Clone 9 hepatocytes. Patch-clamp recording detected GABA-induced currents in Clone 9 hepatocytes and depolarization in WITT cholangiocytes...
December 15, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/27666021/fmrp-regulates-an-ethanol-dependent-shift-in-gababr-function-and-expression-with-rapid-antidepressant-properties
#9
Sarah A Wolfe, Emily R Workman, Chelcie F Heaney, Farr Niere, Sanjeev Namjoshi, Luisa P Cacheaux, Sean P Farris, Michael R Drew, Boris V Zemelman, R Adron Harris, Kimberly F Raab-Graham
Alcohol promotes lasting neuroadaptive changes that may provide relief from depressive symptoms, often referred to as the self-medication hypothesis. However, the molecular/synaptic pathways that are shared by alcohol and antidepressants are unknown. In the current study, acute exposure to ethanol produced lasting antidepressant and anxiolytic behaviours. To understand the functional basis of these behaviours, we examined a molecular pathway that is activated by rapid antidepressants. Ethanol, like rapid antidepressants, alters γ-aminobutyric acid type B receptor (GABABR) expression and signalling, to increase dendritic calcium...
September 26, 2016: Nature Communications
https://www.readbyqxmd.com/read/27553899/auditory-thalamic-circuits-and-gabaa-receptor-function-putative-mechanisms-in-tinnitus-pathology
#10
REVIEW
Donald M Caspary, Daniel A Llano
Tinnitus is defined as a phantom sound (ringing in the ears), and can significantly reduce the quality of life for those who suffer its effects. Ten to fifteen percent of the general adult population report symptoms of tinnitus with 1-2% reporting that tinnitus negatively impacts their quality of life. Noise exposure is the most common cause of tinnitus and the military environment presents many challenging high-noise situations. Military noise levels can be so intense that standard hearing protection is not adequate...
August 21, 2016: Hearing Research
https://www.readbyqxmd.com/read/27552836/prefrontal-cortical-gabaergic-dysfunction-contributes-to-aberrant-up-state-duration-in-app-knockout-mice
#11
Qingwei Huo, Ming Chen, Quansheng He, Jiajia Zhang, Bo Li, Kai Jin, Xi Chen, Cheng Long, Li Yang
Genetic and biochemical studies have focused on the role of amyloid β protein in the pathogenesis of Alzheimer's disease. In comparison, the physiological roles of its precursor protein, amyloid precursor protein (APP), in synaptic and network activity is less well studied. Using an APP knockout (APP(-/-)) mouse model, we show that the duration of UP state, which is a key feature of cortical synaptic integration occurring predominantly during slow-wave sleep, is significantly increased in the prefrontal cortex (PFC) in the absence of APP...
August 23, 2016: Cerebral Cortex
https://www.readbyqxmd.com/read/27511004/gabab-receptors-tune-cortical-feedback-to-the-olfactory-bulb
#12
Camille Mazo, Gabriel Lepousez, Antoine Nissant, Matthew T Valley, Pierre-Marie Lledo
UNLABELLED: Sensory perception emerges from the confluence of sensory inputs that encode the composition of external environment and top-down feedback that conveys information from higher brain centers. In olfaction, sensory input activity is initially processed in the olfactory bulb (OB), serving as the first central relay before being transferred to the olfactory cortex. In addition, the OB receives dense connectivity from feedback projections, so the OB has the capacity to implement a wide array of sensory neuronal computation...
August 10, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27498877/phospho-dependent-accumulation-of-gababrs-at-presynaptic-terminals-after-nmdar-activation
#13
Saad Hannan, Kim Gerrow, Antoine Triller, Trevor G Smart
Here, we uncover a mechanism for regulating the number of active presynaptic GABAB receptors (GABABRs) at nerve terminals, an important determinant of neurotransmitter release. We find that GABABRs gain access to axon terminals by lateral diffusion in the membrane. Their relative accumulation is dependent upon agonist activation and the presence of the two distinct sushi domains that are found only in alternatively spliced GABABR1a subunits. Following brief activation of NMDA receptors (NMDARs) using glutamate, GABABR diffusion is reduced, causing accumulation at presynaptic terminals in a Ca(2+)-dependent manner that involves phosphorylation of GABABR2 subunits at Ser783...
August 16, 2016: Cell Reports
https://www.readbyqxmd.com/read/27468917/selective-ablation-of-girk-channels-in-dopamine-neurons-alters-behavioral-effects-of-cocaine-in-mice
#14
Nora M McCall, Lydia Kotecki, Sergio Dominguez-Lopez, Ezequiel Marron Fernandez de Velasco, Nicholas Carlblom, Amanda L Sharpe, Michael J Beckstead, Kevin Wickman
The increase in dopamine (DA) neurotransmission stimulated by in vivo cocaine exposure is tempered by G protein-dependent inhibitory feedback mechanisms in DA neurons of the ventral tegmental area (VTA). G protein-gated inwardly rectifying K(+) (GIRK/Kir3) channels mediate the direct inhibitory effect of GABAB receptor (GABABR) and D2 DA receptor (D2R) activation in VTA DA neurons. Here we examined the effect of the DA neuron-specific loss of GIRK channels on D2R-dependent regulation of VTA DA neuron excitability and on cocaine-induced, reward-related behaviors...
February 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/27450643/antibody-associated-epilepsies-clinical-features-evidence-for-immunotherapies-and-future-research-questions
#15
REVIEW
Ochuko D Bakpa, Markus Reuber, Sarosh R Irani
PURPOSE: The growing recognition of epilepsies and encephalopathies associated with autoantibodies against surface neuronal proteins (LGI1, NMDAR, CASPR2, GABABR, and AMPAR) means that epileptologists are increasingly asking questions about mechanisms of antibody-mediated epileptogenesis, and about the use of immunotherapies. This review summarizes clinical and paraclinical observations related to autoimmune epilepsies, examines the current evidence for the effectiveness of immunotherapy, and makes epilepsy-specific recommendations for future research...
October 2016: Seizure: the Journal of the British Epilepsy Association
https://www.readbyqxmd.com/read/27299786/-clinical-phenomenology-of-autoimmune-encephalitis
#16
J F Holle, F Jessen, J Kuhn
Antibody-associated disorders of the central nervous system constitute a heterogeneous group of disorders that can be roughly divided into two categories: Classic paraneoplastic syndromes associated with so-called well-characterized antibodies (paraneoplastic neurological disorders, PND) and autoimmune disorders with antibodies to membrane-bound or synaptic antigens (autoimmune encephalitis, AE). The discovery of autoimmune encephalitis has led to a paradigm shift in diagnosis and therapy as well as a reclassification of some neuropsychiatric syndromes that were previously classified as idiopathic or simply covered with descriptive terms...
May 2016: Fortschritte der Neurologie-Psychiatrie
https://www.readbyqxmd.com/read/27294196/gaba-receptors-on-orexin-and-melanin-concentrating-hormone-neurons-are-differentially-homeostatically-regulated-following-sleep-deprivation
#17
Hanieh Toossi, Esther Del Cid-Pellitero, Barbara E Jones
Though overlapping in distribution through the hypothalamus, orexin (Orx) and melanin-concentrating hormone (MCH) neurons play opposite roles in the regulation of sleep-wake states. Orx neurons discharge during waking, whereas MCH neurons discharge during sleep. In the present study, we examined in mice whether GABAA and GABAB receptors (Rs) are present on Orx and MCH neurons and might undergo differential changes as a function of their different activities following sleep deprivation (SD) and sleep recovery (SR)...
May 2016: ENeuro
https://www.readbyqxmd.com/read/27242441/anti-gad65-containing-cerebrospinal-fluid-does-not-alter-gabaergic-transmission
#18
Jana K Hackert, Lorenz Müller, Marco Rohde, Christian G Bien, Rüdiger Köhling, Timo Kirschstein
Glutamic acid decarboxylase of 65 kDa (GAD65) antibodies have been reported in a variety of neurological disorders such as stiff-person syndrome (SPS), sporadic ataxia and some cases of epilepsy. Since the target is believed to be the cytoplasmic enzyme GAD65, the key enzyme of γ-aminobutyric acid (GABA) synthesis, the pathophysiological role of these antibodies is poorly understood. Here, we stereotactically injected human cerebrospinal fluid (CSF) containing GAD65-antibodies into the hippocampus of rats in vivo and then prepared hippocampal slices 1-2 days after post-operative recovery...
2016: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/27225074/somatostatin-expressing-neurons-in-cortical-networks
#19
REVIEW
Joanna Urban-Ciecko, Alison L Barth
Somatostatin-expressing GABAergic neurons constitute a major class of inhibitory neurons in the mammalian cortex and are characterized by dense wiring into the local network and high basal firing activity that persists in the absence of synaptic input. This firing provides both GABA type A receptor (GABAAR)- and GABABR-mediated inhibition that operates at fast and slow timescales. The activity of somatostatin-expressing neurons is regulated by brain state, during learning and in rewarded behaviour. Here, we review recent advances in our understanding of how this class of cells can control network activity, with specific reference to how this is constrained by their anatomical and electrophysiological properties...
2016: Nature Reviews. Neuroscience
https://www.readbyqxmd.com/read/27112679/anti-nmdar-encephalitis-and-other-glutamate-and-gaba-receptor-antibody-encephalopathies
#20
Marienke A A M De Bruijn, Maarten J Titulaer
Over the last few year, antibodies to various central nervous system receptors, particularly the glutamate and γ-aminobutyric acid (GABA) receptors, have been found to be associated with autoimmune neurologic disorders. The receptors include the N-methyl-d-aspartate receptor (NMDAR), the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR), the metabotropic glutamate receptors (mGluRs), and GABA type A and B receptors (respectively GABAAR and GABABR). Compared to the previously described paraneoplastic antibodies directed at intracellular targets, the patients with receptor antibodies are often younger, they less frequently have malignancies, and they respond better to immunotherapy...
2016: Handbook of Clinical Neurology
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