keyword
https://read.qxmd.com/read/38484926/the-role-of-astrocytic-%C3%AE-aminobutyric-acid-in-the-action-of-inhalational-anesthetics
#21
JOURNAL ARTICLE
Dongwook Won, Elliot H Lee, Jee-Eun Chang, Min-Ho Nam, Ki Duk Park, Soo-Jin Oh, Jin-Young Hwang
BACKGROUND: Inhalational anesthetics target the inhibitory extrasynaptic γ-aminobutyric acid type A (GABAA ) receptors. Both neuronal and glial GABA mediate tonic inhibition of the extrasynaptic GABAA receptors. However, the role of glial GABA during inhalational anesthesia remains unclear. This study aimed to evaluate whether astrocytic GABA contributes to the action of different inhalational anesthetics. METHODS: Gene knockout of monoamine oxidase B (MAOB) was used to reduce astrocytic GABA levels in mice...
March 12, 2024: European Journal of Pharmacology
https://read.qxmd.com/read/38468966/exploring-antioxidative-cytotoxic-and-neuropharmacological-insights-into-bixa-orellana-leaves-experimental-and-in-silico-approaches
#22
JOURNAL ARTICLE
Kishore Kumar Sarkar, Trina Mitra, Md Aktaruzzaman, Md Ahsan Abid, Md Asibur Rahman, Pradip Debnath, Samir Kumar Sadhu
BACKGROUND STUDY: The aim of this research was to examine possible antioxidant, cytotoxic and neurological activity of methanol and n-hexane extracts of Bixa orellana leaves. Additionally, we aimed to identify potential lead compounds through in-silico analysis. METHODS: In-vitro antioxidative properties were investigated through different assays, including: total phenolic content assay (TPC), total flavonoid content assay (TFC), DPPH free radical scavenging assay and reducing power assay...
March 15, 2024: Heliyon
https://read.qxmd.com/read/38468526/increased-cyclic-adenosine-monophosphate-responsive-element-is-closely-associated-with-the-pathogenesis-of-drug-resistant-epilepsy
#23
JOURNAL ARTICLE
Jing-Xuan Li, Dai Shi, Si-Ying Ren, Guo-Feng Wu
BACKGROUND: Drug-resistant epilepsy (DRE) is a refractory neurological disorder. There is ample evidence that suggest that γ-aminobutyric acid-a (GABAA) receptors could be one of the mechanisms responsible for the development of drug resistance in epilepsy. It is also known that the cAMP response element binding protein (CREB) plays a possible key role in the transcriptional regulation of GABAA. OBJECTIVE: This study explores the role of CREB in the development of DRE and the effect of CREB on GABA-related receptors in DRE...
March 8, 2024: Current Neurovascular Research
https://read.qxmd.com/read/38449810/established-and-emerging-gaba-a-receptor-pharmacotherapy-for-epilepsy
#24
REVIEW
Robert J Richardson, Steven Petrou, Alexander Bryson
Drugs that modulate the GABAA receptor are widely used in clinical practice for both the long-term management of epilepsy and emergency seizure control. In addition to older medications that have well-defined roles for the treatment of epilepsy, recent discoveries into the structure and function of the GABAA receptor have led to the development of newer compounds designed to maximise therapeutic benefit whilst minimising adverse effects, and whose position within the epilepsy pharmacologic armamentarium is still emerging...
2024: Frontiers in Pharmacology
https://read.qxmd.com/read/38447577/phasic-tonic-glial-gaba-differentially-transduce-for-olfactory-adaptation-and-neuronal-aging
#25
JOURNAL ARTICLE
Hankui Cheng, Du Chen, Xiao Li, Umar Al-Sheikh, Duo Duan, Yuedan Fan, Linhui Zhu, Wanxin Zeng, Zhitao Hu, Xiajing Tong, Guohua Zhao, Yongming Zhang, Wenjuan Zou, Shumin Duan, Lijun Kang
Phasic (fast) and tonic (sustained) inhibition of γ-aminobutyric acid (GABA) are fundamental for regulating day-to-day activities, neuronal excitability, and plasticity. However, the mechanisms and physiological functions of glial GABA transductions remain poorly understood. Here, we report that the AMsh glia in Caenorhabditis elegans exhibit both phasic and tonic GABAergic signaling, which distinctively regulate olfactory adaptation and neuronal aging. Through genetic screening, we find that GABA permeates through bestrophin-9/-13/-14 anion channels from AMsh glia, which primarily activate the metabolic GABAB receptor GBB-1 in the neighboring ASH sensory neurons...
March 1, 2024: Neuron
https://read.qxmd.com/read/38443647/an-update-on-stiripentol-mechanisms-of-action-a-narrative-review
#26
REVIEW
Alexandre Bacq, Antoine Depaulis, Vincent Castagné, Marie-Emmanuelle Le Guern, Elaine C Wirrell, Marc Verleye
Stiripentol (Diacomit® ) (STP) is an orally active antiseizure medication (ASM) indicated as adjunctive therapy, for the treatment of seizures associated with Dravet syndrome (DS), a severe form of childhood epilepsy, in conjunction with clobazam and, in some regions valproic acid. Since the discovery of STP, several mechanisms of action (MoA) have been described that may explain its specific effect on seizures associated with DS. STP is mainly considered as a potentiator of gamma-aminobutyric acid (GABA) neurotransmission: (i) via uptake blockade, (ii) inhibition of degradation, but also (iii) as a positive allosteric modulator of GABAA receptors, especially those containing α3 and δ subunits...
March 5, 2024: Advances in Therapy
https://read.qxmd.com/read/38440939/pharmacokinetics-and-exposure-safety-relationship-of-ciprofol-for-sedation-in-mechanically-ventilated-patients-in-the-intensive-care-unit
#27
JOURNAL ARTICLE
Lu Liu, Kun Wang, Zhongyi Sun, Pangke Yan, Mengyue Hu, Xiao Liu, Meixia Chen, Nan Wu, Xiaoqiang Xiang
Ciprofol (HSK3486) is a newly developed, highly selective γ-aminobutyric acid-A (GABAA ) receptor potentiator that is recently approved for a new indication of sedation for patients in the intensive care unit (ICU) in China. This analysis aimed to characterize the population pharmacokinetics (PopPKs) of ciprofol and evaluate the relationship of exposure with hypotension in mechanically ventilated patients in the ICU. A total of 462 subjects with 3918 concentration measurements from two clinical trials of mechanically ventilated patients in the ICU, four clinical trials of elective surgical patients, and six clinical trials of healthy subjects were used in the PopPK analysis...
March 5, 2024: CPT: Pharmacometrics & Systems Pharmacology
https://read.qxmd.com/read/38431842/gaba-co-released-from-striatal-dopamine-axons-dampens-phasic-dopamine-release-through-autoregulatory-gaba-a-receptors
#28
JOURNAL ARTICLE
Jyoti C Patel, Ang D Sherpa, Riccardo Melani, Paul Witkovsky, Madeline R Wiseman, Brian O'Neill, Chiye Aoki, Nicolas X Tritsch, Margaret E Rice
Striatal dopamine axons co-release dopamine and gamma-aminobutyric acid (GABA), using GABA provided by uptake via GABA transporter-1 (GAT1). Functions of GABA co-release are poorly understood. We asked whether co-released GABA autoinhibits dopamine release via axonal GABA type A receptors (GABAA Rs), complementing established inhibition by dopamine acting at axonal D2 autoreceptors. We show that dopamine axons express α3-GABAA R subunits in mouse striatum. Enhanced dopamine release evoked by single-pulse optical stimulation in striatal slices with GABAA R antagonism confirms that an endogenous GABA tone limits dopamine release...
March 1, 2024: Cell Reports
https://read.qxmd.com/read/38428397/rapid-simulation-of-glycoprotein-structures-by-grafting-and-steric-exclusion-of-glycan-conformer-libraries
#29
JOURNAL ARTICLE
Yu-Xi Tsai, Ning-En Chang, Klaus Reuter, Hao-Ting Chang, Tzu-Jing Yang, Sören von Bülow, Vidhi Sehrawat, Noémie Zerrouki, Matthieu Tuffery, Michael Gecht, Isabell Louise Grothaus, Lucio Colombi Ciacchi, Yong-Sheng Wang, Min-Feng Hsu, Kay-Hooi Khoo, Gerhard Hummer, Shang-Te Danny Hsu, Cyril Hanus, Mateusz Sikora
Most membrane proteins are modified by covalent addition of complex sugars through N- and O-glycosylation. Unlike proteins, glycans do not typically adopt specific secondary structures and remain very mobile, shielding potentially large fractions of protein surface. High glycan conformational freedom hinders complete structural elucidation of glycoproteins. Computer simulations may be used to model glycosylated proteins but require hundreds of thousands of computing hours on supercomputers, thus limiting routine use...
February 29, 2024: Cell
https://read.qxmd.com/read/38428383/structural-basis-for-molecular-recognition-of-cannabinoids-by-inhibitory-cys-loop-channels
#30
REVIEW
Lautaro D Alvarez, N R Carina Alves
Cannabis sativa has a long history of medicinal use, dating back to ancient times. This plant produces cannabinoids, which are now known to interact with several human proteins, including Cys-loop receptors for glycine (GlyR) and gamma-aminobutyric acid (GABAA R). As these channels are the primary mediators of inhibitory signals, they contribute to the diverse effects of cannabinoids on the nervous system. Evidence suggests that cannabinoid binding sites are located within the transmembrane domain, although their precise location has remained undetermined for over a decade...
March 14, 2024: Journal of Medicinal Chemistry
https://read.qxmd.com/read/38423391/potential-of-the-blue-calm%C3%A2-food-supplement-in-the-treatment-of-alcohol-withdrawal-induced-anxiety-in-adult-zebrafish-danio-rerio
#31
JOURNAL ARTICLE
Luzia Débora S Marques, Yatagan Moreira da Rocha, Gabriela A do Nascimento, Sacha Aubrey A R Santos, Natália Chaves Gondim Vieira, Luiz Francisco Wemmenson Gonçalves Moura, Daniela Ribeiro Alves, Wildson Max Barbosa da Silva, Selene M de Morais, Keciany Alves de Oliveira, Larissa Morais Ribeiro da Silva, Kalina Kelma Oliveira de Sousa, Antonio Eufrásio Vieira-Neto, Henrique Douglas Melo Coutinho, Adriana R Campos, Francisco Ernani A Magalhães
Alcohol use disorder (AUD) is characterized by a set of behavioral, cognitive, nutritional, and physiological phenomena derived from the uncontrolled use of alcoholic beverages. There are cases in which AUD is associated with anxiety disorder, and when untreated, it requires careful pharmacotherapy. Blue Calm® (BC) is a food supplement indicated to aid restorative sleep, which has traces of medicinal plant extracts, as well as myo-inositol, magnesium bisglycinate, taurine, and L-tryptophan as its main chemical constituents...
February 27, 2024: Neurochemistry International
https://read.qxmd.com/read/38421468/ivermectin-exerts-anticonvulsant-effects-against-status-epilepticus-induced-by-lithium-pilocarpine-in-rats-via-gaba-a-receptor-and-neuroinflammation-modulation-possible-interaction-of-opioidergic-pathways-and-k-atp-channel-with-nitrergic-system
#32
JOURNAL ARTICLE
Mohammad Amin Manavi, Samaneh Toutounchian, Sahar Afsahi, Zahra Ebrahim Soltani, Razieh Mohammad Jafari, Ahmad Reza Dehpour
Status epilepticus (SE) is a critical medical emergency marked by persistent or rapidly repeating seizures, posing a threat to life. Using the lithium-pilocarpine-induced SE model, we decide to evaluate the anti-seizure effects of ivermectin as a positive allosteric modulator of GABAA receptor and the underlying mechanisms involved. Lithium chloride was injected intraperitoneally at a dose of 127 mg/kg, followed by the administration of pilocarpine at a dose of 60 mg/kg after a 20-h interval in order to induce SE...
February 29, 2024: Molecular Neurobiology
https://read.qxmd.com/read/38417289/electroencephalographic-profile-of-salvia-amarissima-ortega-and-amarisolide-a-in-the-absence-and-presence-of-ptz-induced-seizures-in-mice
#33
JOURNAL ARTICLE
Rodrigo Mendoza-Madrigal, María Eva González-Trujano, Daniela Onofre-Campos, Gabriel Fernando Moreno-Pérez, Jazmin Guadalupe Castellanos-Mijangos, David Martínez-Vargas
Salvia amarissima Ortega is a plant used in traditional medicine to treat CNS's affections. Despite its depressant properties in anxiety and fibromyalgia, there is no scientific evidence about its capability to control seizure activity. This study aimed to investigate the effects of the S. amarissima aqueous extract (SAAE) and its metabolite amarisolide A (AMA) on the electrocorticographic (ECoG) activity. The ECoG profiles were previously and concurrently analyzed to the pentylenetetrazole (85 mg/kg, i...
February 27, 2024: Biomedicine & Pharmacotherapy
https://read.qxmd.com/read/38415182/synergistic-effect-between-citalopram-and-muscimol-upon-induction-of-anxiolytic-and-antidepressant-like-effects-in-male-mice-an-isobologram-analysis
#34
JOURNAL ARTICLE
Elnaz Amini, Taha Shokrnejad-Namin, Mohammad-Reza Zarrindast, Fatemeh Khakpai
BACKGROUND: There is evidence that both the GABAergic system and serotonin reuptake inhibitor (SSRI) such as citalopram are involved in the modulation of anxiety and depression processes. In this research, we examined the effects of GABAA receptor agents and citalopram on anxiety- and depression-related behaviors and their interaction in male mice. METHODS: For intracerebroventricular (i.c.v.) infusion, a guide cannula was implanted in the left lateral ventricle...
June 2024: IBRO neuroscience reports
https://read.qxmd.com/read/38414297/quercetin-increases-the-antidepressant-like-effects-of-sclareol-and-antagonizes-diazepam-in-thiopental-sodium-induced-sleeping-mice-a-possible-gabaergic-transmission-intervention
#35
JOURNAL ARTICLE
Mehedi Hasan Bappi, Md Nayem Mia, Siddique Akber Ansari, Irfan Aamer Ansari, Abdullah Al Shamsh Prottay, Md Showkoth Akbor, Heba A S El-Nashar, Mohamed El-Shazly, Mohammad S Mubarak, Muhammad Torequl Islam
Quercetin is the most common polyphenolic flavonoid present in fruits and vegetables demonstrating versatile health-promoting effects. This study aimed to examine the effects of quercetin (QR) and sclareol (SCL) on the thiopental sodium (TS)-induced sleeping and forced swimming test (FST) mouse models. SCL (1, 5, and 10 mg/kg, p.o.) or QR (50 mg/kg, p.o.) and/or diazepam (DZP) (3 mg/kg, i.p.) were employed. After 30 min of TS induction, individual or combined effects on the animals were checked...
February 27, 2024: Phytotherapy Research: PTR
https://read.qxmd.com/read/38413230/t-type-ca-2-channels-mediate-a-critical-period-of-plasticity-in-adult-born-granule-cells
#36
JOURNAL ARTICLE
William M Kennedy, Jose Carlos Gonzalez, Haeun Lee, Jacques I Wadiche, Linda Overstreet-Wadiche
Adult-born granule cells (abGCs) exhibit a transient period of elevated synaptic plasticity that plays an important role in hippocampal function. Various mechanisms have been implicated in this critical period for enhanced plasticity, including minimal GABAergic inhibition and high intrinsic excitability conferred by T-type Ca2+ channels. Here we assess the contribution of synaptic inhibition and intrinsic excitability to long-term potentiation (LTP) in abGCs of adult male and female mice using perforated patch recordings...
February 27, 2024: Journal of Neuroscience
https://read.qxmd.com/read/38413199/extrasynaptic-localization-is-essential-for-%C3%AE-5gaba-a-receptor-modulation-of-dopamine-system-function
#37
JOURNAL ARTICLE
Alexandra M McCoy, Thomas D Prevot, Md Yeunus Mian, Dishary Sharmin, Adeeba N Ahmad, James M Cook, Etienne L Sibille, Daniel J Lodge
Dopamine system dysfunction, observed in animal models with psychosis-like symptomatology, can be restored by targeting Gamma-Aminobutyric Acid type A receptors (GABAA R) containing the α5, but not α1, subunit in the ventral hippocampus (vHipp). The reason for this discrepancy in efficacy remains elusive; however, one key difference is that α1GABAA Rs are primarily located in the synapse, whereas α5GABAA Rs are mostly extrasynaptic. To test whether receptor location is responsible for this difference in efficacy, we injected a small interfering ribonucleic acid (siRNA) into the vHipp to knock down radixin, a scaffolding protein that holds α5GABAA Rs in the extrasynaptic space...
February 27, 2024: ENeuro
https://read.qxmd.com/read/38412941/exploring-the-clinical-potentials-of-zuranolone-in-managing-postpartum-depression-a-new-therapeutic-horizon
#38
JOURNAL ARTICLE
Abdulqadir J Nashwan, Syeda Tayyaba Rehan, Laiba Imran, Samina Ghulam Abbas, Sara Fahim Khan
Postpartum depression (PPD) poses a major threat to maternal mental health and wellbeing while also adversely affecting the mother's relationship with her baby, leading to significant repercussions that may hinder the growth and cognitive development of the child. For decades, antidepressants have been the mainstay of treating PPD; however, recent evidence suggests that antidepressants are not as effective as they are believed to be and there is a dire need to explore new treatment options. In 2023, a breakthrough in treating PPD emerged with the recent FDA approval of zuranolone, a gamma-aminobutyric acid (GABAA ) receptor selective positive allosteric modulator...
February 25, 2024: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://read.qxmd.com/read/38411499/the-anterior-retrosplenial-cortex-is-required-for-short-term-object-in-place-recognition-memory-retrieval-role-of-ionotropic-glutamate-receptors-in-male-and-female-long-evans-rats
#39
JOURNAL ARTICLE
Dan L McElroy, Hassaan Sabir, Aiden E Glass, Quentin Greba, John G Howland
The anterior retrosplenial cortex (aRSC) integrates multimodal sensory information into cohesive associative recognition memories. Little is known about how information is integrated during different learning phases (i.e., encoding and retrieval). Additionally, sex differences are observed in performance of some visuospatial memory tasks; however, inconsistent findings warrant more research. We conducted three experiments using the 1-h delay object-in-place (1-h OiP) test to assess recognition memory retrieval in male and female Long-Evans rats...
February 27, 2024: European Journal of Neuroscience
https://read.qxmd.com/read/38400541/gaba-a-receptor-subunit-m2-m3-linkers-have-asymmetric-roles-in-pore-gating-and-diazepam-modulation
#40
JOURNAL ARTICLE
Joseph W Nors, Zachary Endres, Marcel P Goldschen-Ohm
GABAA receptors (GABAA Rs) are neurotransmitter-gated ion channels critical for inhibitory synaptic transmission as well as the molecular target for benzodiazepines (BZDs), one of the most widely prescribed class of psychotropic drugs today. Despite structural insight into the conformations underlying functional channel states, the detailed molecular interactions involved in conformational transitions and the physical basis for their modulation by BZDs are not fully understood. We previously identified that alanine substitution at the central residue in the α1 subunit M2-M3 linker (V279A) enhances the efficiency of linkage between the BZD site and the pore gate...
February 22, 2024: Biophysical Journal
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