scholarly journals Is It Feasible of Prophylactic Alpha-5 GABA(A) Receptor Blockade for Preventing POCD?

2013 ◽  
Vol 3 (3) ◽  
pp. 61-62
Author(s):  
Fuzhou Wang
Keyword(s):  
Nervous System ◽  
General Anesthesia ◽  
Neuronal Excitability ◽  
Underlying Mechanism ◽  
Gamma Aminobutyric Acid ◽  
Gaba A ◽  
Inhibitory Neurotransmitter ◽  
Inhalational Anesthetics ◽  
Exploratory Data

GAMMA-AMINOBUTYRIC ACID (GABA) is the chief inhibitory neurotransmitter in the mammalian central nervous system (CNS). It plays a role in regulating neuronal excitability throughout the nervous system. Also GABA activation is considered as the basis of general anesthesia including intravenous and inhalational anesthetics. Meanwhile, cumulating evidence indicated that GABA is the underlying mechanism of post-operative cognitive dysfunction (POCD). Based on these findings, researchers are beginning to focus on GABA as the target to treat POCD, but they ignored the role of GABA in the performance of general anesthesia, especially when the blockade of GABA was given prior to surgery. It is undoubtedly risking our patients in intra-operative awareness. Our exploratory data also verified our hypothesis in which the GABA inhibition would reduce the efficacy of inhalational anesthetics.

The role of GABA in modulating the Xenopus electroretinogram

1997 ◽  
Vol 14 (6) ◽  
pp. 1143-1152 ◽  
Author(s):  
Arsaell Arnarsson ◽  
Thor Eysteinsson
Keyword(s):  
Light Sensitivity ◽  
Gaba Uptake ◽  
Peak Time ◽  
Gamma Aminobutyric Acid ◽  
Nipecotic Acid ◽  
Gaba A ◽  
Inhibitory Neurotransmitter ◽  
Retinal Circuitry ◽  
Gaba Antagonist

AbstractWe have recorded the electroretinogram (ERG) from the superfused eyecup of the Xenopus retina in order to assess the effects of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), and its agonists and antagonists, on individual ERG components. We found that GABA (0.5–10 mM) reduced the amplitudes of both the b- and d-waves of the Xenopus ERG. The GABA uptake blocker nipecotic acid (1 mM) had similar effects on b- and d-waves. GABA at 5 mM and 10 mM also caused an increase in the a-wave. The GABA antagonist picrotoxin (0.1–2 mM) and the GABA/a antagonist bicuculline (0.2 mM) both increased the amplitude of the b- and d-waves of the ERG. The GABA/b agonist baclofen (0.3 mM) reduced the amplitude of the ERG b-wave, enhanced the amplitude of the a-wave, and slightly reduced the amplitude and increased the peak time of the d-wave. The GABA/b antagonists phaclofen and saclofen had no reliable effects on the Xenopus ERG. Glutamate analogs known to affect specific types of retinal neurons were applied to modify the retinal circuitry and then the effects of GABA and its antagonists were examined under these modified conditions. 2-amino-4-phosphonobutyric acid (APB) increased the d-wave, and blocked the b-wave and the effect of GABA on the ERG, but not the antagonist-induced increase in the d-wave. KYN blocked the antagonist-induced increase in the b-wave, while GABA increases the amplitude of the b-wave if the d-wave has been removed by prior superfusion with kynurenic acid (KYN). N-methyl-DL-aspartate (NMDLA), which acts only in the proximal retina, reduced the amplitude of the ERG and blocked the effect of GABA and the antagonist-induced increase in ERG b- and d-waves amplitude. These results suggest that GABAergic mechanisms related to both A and B receptor types can influence the amplitude and light sensitivity of all the components of the Xenopus ERG. Since GABA is found in greatest abundance in the proximal retina, and B type of receptors are present almost exclusively there, the data suggests that most of the effects of GABA agonists and antagonists observed are dependent on proximal retinal mechanisms, and that there are separate mechanisms in the proximal retina related to the b- and the d-waves.

scholarly journals The role of γ-aminobutyric acid in aluminum stress tolerance in a woody plant, Liriodendron chinense × tulipifera

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Pengkai Wang ◽  
Yini Dong ◽  
Liming Zhu ◽  
Zhaodong Hao ◽  
LingFeng Hu ◽  
...  
Keyword(s):  
Woody Plant ◽  
Underlying Mechanism ◽  
Absolute Quantification ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Aluminum Stress ◽  
Inhibitory Neurotransmitter ◽  
Al Stress ◽  
Protein Ubiquitination ◽  
Liriodendron Chinense

AbstractThe aluminum (Al) cation Al3+ in acidic soil shows severe rhizotoxicity that inhibits plant growth and development. Most woody plants adapted to acidic soils have evolved specific strategies against Al3+ toxicity, but the underlying mechanism remains elusive. The four-carbon amino acid gamma-aminobutyric acid (GABA) has been well studied in mammals as an inhibitory neurotransmitter; GABA also controls many physiological responses during environmental or biotic stress. The woody plant hybrid Liriodendron (L. chinense × tulipifera) is widely cultivated in China as a horticultural tree and provides high-quality timber; studying its adaptation to high Al stress is important for harnessing its ecological and economic potential. Here, we performed quantitative iTRAQ (isobaric tags for relative and absolute quantification) to study how protein expression is altered in hybrid Liriodendron leaves subjected to Al stress. Hybrid Liriodendron shows differential accumulation of several proteins related to cell wall biosynthesis, sugar and proline metabolism, antioxidant activity, cell autophagy, protein ubiquitination degradation, and anion transport in response to Al damage. We observed that Al stress upregulated glutamate decarboxylase (GAD) and its activity, leading to increased GABA biosynthesis. Additional GABA synergistically increased Al-induced antioxidant enzyme activity to efficiently scavenge ROS, enhanced proline biosynthesis, and upregulated the expression of MATE1/2, which subsequently promoted the efflux of citrate for chelation of Al3+. We also showed similar effects of GABA on enhanced Al3+ tolerance in Arabidopsis. Thus, our findings suggest a function of GABA signaling in enhancing hybrid Liriodendron tolerance to Al stress through promoting organic acid transport and sustaining the cellular redox and osmotic balance.

scholarly journals GABA receptors differentially regulate life span and health span in C. elegans through distinct downstream mechanisms

2019 ◽  
Vol 317 (5) ◽  
pp. C953-C963 ◽  
Author(s):  
Fengling Yuan ◽  
Jiejun Zhou ◽  
Lingxiu Xu ◽  
Wenxin Jia ◽  
Lei Chun ◽  
...  
Keyword(s):  
Life Span ◽  
Gaba Receptors ◽  
Health Span ◽  
Gaba A ◽  
Inhibitory Neurotransmitter ◽  
C Elegans ◽  
Physiological Processes ◽  
Gaba Signaling ◽  
Neuronal Functions

GABA, a prominent inhibitory neurotransmitter, is best known to regulate neuronal functions in the nervous system. However, much less is known about the role of GABA signaling in other physiological processes. Interestingly, recent work showed that GABA signaling can regulate life span via a metabotropic GABAB receptor in Caenorhabditis elegans. However, the role of other types of GABA receptors in life span has not been clearly defined. It is also unclear whether GABA signaling regulates health span. Here, using C. elegans as a model, we systematically interrogated the role of various GABA receptors in both life span and health span. We find that mutations in four different GABA receptors extend health span by promoting resistance to stress and pathogen infection and that two such receptor mutants also show extended life span. Different GABA receptors engage distinct transcriptional factors to regulate life span and health span, and even the same receptor regulates life span and health span via different transcription factors. Our results uncover a novel, profound role of GABA signaling in aging in C. elegans, which is mediated by different GABA receptors coupled to distinct downstream effectors.

scholarly journals Activation of central 5-HT2A receptor in brain inhibited the seizure-induced respiratory arrest in the DBA/1 mouse SUDEP model

2020 ◽  
Author(s):  
Yue Shen ◽  
HaiXiang Ma ◽  
XiTing Lian ◽  
LeYuan Gu ◽  
Qian Yu ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Drug Resistance ◽  
Nervous System ◽  
Underlying Mechanism ◽  
Respiratory Arrest ◽  
Acoustic Stimulation ◽  
Unexpected Death ◽  
Anti Epileptic Drug ◽  
The Brain

AbstractSudden unexpected death in epilepsy (SUDEP) is the fatal cause leading to the death of epilepsy patients with anti-epileptic drug resistance. However, the underlying mechanism of SUDEP remains to be elusive. Our previous study demonstrated that enhancement of serotonin (5-HT) synthesis by intraperitoneal (IP) injection of 5-hydroxytryptophan in brain significantly reduced the incidence of seizure-induced respiratory arrest (S-IRA) in DBA/1 mice SUDEP models. Given that 5-HT2A receptor (5-HT2AR) acts an important role in mediating respiration system in brain, we hypothesized that 5-HT2AR is of great significance to modulate S-IRA and SUDEP. To test this hypothesis, we examined whether the decreased incidence S-IRA evoked by either acoustic stimulation or PTZ by blocking 5-HT2AR by administration with ketanserin (KET), a selective antagonist of 5HT2AR, in DBA/1 mice SUDEP models to test the role of 5-HT2AR modulating S-IRA. Our results suggested that the decreased incidence of S-IRA by 5-Hydroxytryptophan (5-HTP), a precursor for central nervous system (CNS) serotonin (5-HT) synthesis, was significantly reversed by IP and intracerebroventricularly (ICV) injection of ketanserin in our models. Thus, our data suggested that 5-HT2AR in the brain may be a potential and specific target to prevent SUDEP.

Glial Cells and Pro-inflammatory Cytokines as Shared Neurobiological Bases for Chronic Pain and Psychiatric Disorders

2020 ◽  
pp. 27-49
Author(s):  
Judith A. Strong ◽  
Sang Won Jeon ◽  
Jun-Ming Zhang ◽  
Yong-Ku Kim
Keyword(s):  
Chronic Pain ◽  
Nervous System ◽  
Psychiatric Disorders ◽  
Inflammatory Cytokines ◽  
Glial Cells ◽  
Neuronal Excitability ◽  
Pro Inflammatory Cytokines

This chapter reviews the roles of cytokines and glial cells in chronic pain and in psychiatric disorders, especially depression. One important role of cytokines is in communicating between activated glia and neurons, at all levels of the nervous system. This process of neuroinflammation plays important roles in pain and depression. Cytokines may also directly regulate neuronal excitability. Many cytokines have been implicated in both pain and psychiatric disorders, including interleukin-1β‎ (IL-1β‎), tumor necrosis factor-α‎, and IL-6. More generally, an imbalance between type 1, pro-inflammatory cytokines and type 2, anti-inflammatory cytokines has been implicated in both pain and psychiatric disorders. Activation of the sympathetic nervous system can contribute to both pain and psychiatric disorders, in part through its actions on inflammation and the cytokine profile.

scholarly journals Role of the DSC1 Channel in Regulating Neuronal Excitability in Drosophila melanogaster: Extending Nervous System Stability under Stress

PLoS Genetics ◽  
2013 ◽  
Vol 9 (3) ◽  
pp. e1003327 ◽  
Author(s):  
Tianxiang Zhang ◽  
Zhe Wang ◽  
Lingxin Wang ◽  
Ningguang Luo ◽  
Lan Jiang ◽  
...  
Keyword(s):  
Nervous System ◽  
Drosophila Melanogaster ◽  
Neuronal Excitability ◽  
System Stability

Kratom and Future Treatment for the Opioid Addiction and Chronic Pain: Periculo Beneficium?

2018 ◽  
Vol 20 (2) ◽  
pp. 166-172 ◽  
Author(s):  
Ismaliza Ismail ◽  
Suzaily Wahab ◽  
Hatta Sidi ◽  
Srijit Das ◽  
Loo Jiann Lin ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Opioid Receptors ◽  
Underlying Mechanism ◽  
Opioid Addiction ◽  
Gamma Aminobutyric Acid ◽  
Substitution Therapy ◽  
Mitragyna Speciosa ◽  
Reward Pathways ◽  
Potential Use

Kratom (Mitragyna speciosa), a naturally existing plant found in South-East Asia, is traditionally used as a herb to help elevate a person’s energy and also to treat numerous medical ailments. Other than the analgesic property, kratom has been used as an agent to overcome opioid withdrawal as it contains natural alkaloids, i.e. mitragynine, 7-hydroxymitragynine, and MGM-9, which has agonist affinity on the opioid receptors, including mu (µ) and kappa (κ). The role of neural reward pathways linked to µ-opioid receptors and both dopaminergic and gamma-Aminobutyric acid (GABA)-ergic interneurons that express µ-opioid receptors were deliberated. However, kratom has been reported to be abused together with other illicit substances with high risk of potential addiction. There are also anecdotes of adverse effects and toxicity of kratom, i.e. tremor, fatigue, seizure, and death. Different countries have distinctive regulation and policy on the plantation and use of this plant when most of the countries banned the use of it because of its addiction problems and side effects. The aim of this review is to highlight on the potential use of kratom, unique ‘herbs” as a substitution therapy for chronic pain and opioid addiction, based on the neurobiological perspective of pain and the underlying mechanism of actions of drug addiction.

scholarly journals RGS7/Gβ5/R7BP complex regulates synaptic plasticity and memory by modulating hippocampal GABABR-GIRK signaling

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Olga Ostrovskaya ◽  
Keqiang Xie ◽  
Ikuo Masuho ◽  
Ana Fajardo-Serrano ◽  
Rafael Lujan ◽  
...  
Keyword(s):  
Synaptic Plasticity ◽  
Neuronal Excitability ◽  
Pyramidal Neurons ◽  
Dynamic Range ◽  
Gabab Receptor ◽  
Girk Channels ◽  
Hippocampal Pyramidal Neurons ◽  
Inhibitory Neurotransmitter ◽  
Membrane Anchoring

In the hippocampus, the inhibitory neurotransmitter GABA shapes the activity of the output pyramidal neurons and plays important role in cognition. Most of its inhibitory effects are mediated by signaling from GABAB receptor to the G protein-gated Inwardly-rectifying K+ (GIRK) channels. Here, we show that RGS7, in cooperation with its binding partner R7BP, regulates GABABR-GIRK signaling in hippocampal pyramidal neurons. Deletion of RGS7 in mice dramatically sensitizes GIRK responses to GABAB receptor stimulation and markedly slows channel deactivation kinetics. Enhanced activity of this signaling pathway leads to decreased neuronal excitability and selective disruption of inhibitory forms of synaptic plasticity. As a result, mice lacking RGS7 exhibit deficits in learning and memory. We further report that RGS7 is selectively modulated by its membrane anchoring subunit R7BP, which sets the dynamic range of GIRK responses. Together, these results demonstrate a novel role of RGS7 in hippocampal synaptic plasticity and memory formation.

Explaining reflex sympathetic dystrophy

2018 ◽  
Author(s):  
Brigitta Brandner
Keyword(s):  
Nervous System ◽  
Autonomic Nervous System ◽  
Reflex Sympathetic Dystrophy ◽  
Disease Process ◽  
Underlying Mechanism ◽  
Medical Community ◽  
Seminal Paper ◽  
Trophic Changes ◽  
Bone Atrophy

The medical community had long been aware of a constellation of symptoms involving pain, bone atrophy, and trophic changes that could occur following a trauma; however, this paper was the first to unify and explain the syndrome. James Evans amalgamated other theories of the time and was the first to realize the fundamental role of the autonomic nervous system in explaining the pathophysiology of the condition, which he named ‘reflex sympathetic dystrophy’. Evans uses 57 cases histories to highlight the variety of noxious stimuli that may result in reflex sympathetic dystrophy, and goes onto outline the local anaesthetic blocks and sympathectomies he used to treat them. This is a seminal paper because Evans is the first to use the term ‘reflex sympathetic dystrophy’ and, in doing so, proposes an underlying mechanism for a disease process that, while known, was until then very poorly understood.

Neurochemicals and respiratory control during development

1989 ◽  
Vol 67 (1) ◽  
pp. 1-13 ◽  
Author(s):  
I. R. Moss ◽  
J. G. Inman
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Respiratory Control ◽  
Perinatal Period ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Respiratory Effects ◽  
The Central Nervous System ◽  
Plastic Process

During ontogeny, the central nervous system undergoes neuronal growth, regression, and remodeling. The development of neurotransmitter and modulator systems is a plastic process with individual temporal characteristics for each system. These characteristics include the synthesis, degradation, or uptake of neurochemicals and, largely independently, the appearance of their receptors. Message transmission during ontogeny is compounded by the variable development of these systems and by the coexistence and cofunction among these chemicals. Nine neurochemical systems are discussed: adenosine, gamma-aminobutyric acid, opioids, prostaglandins, serotonin, progesterone, substance P, thyrotropin-releasing hormone, and the catecholamines. The possible role of each of these in natural perinatal respiratory control is evaluated according to predetermined criteria. These include the presence of a substance system in respiratory-related regions, physiologically appropriate changes in its concentration in these regions, elicitation of respiratory effects by agonists and antagonists, and abolition with an antagonist of the effect of a substance during its presumed activation by a physiological process. It is suggested that excessive levels of suppressant neuromodulators or an imbalance among neurochemicals can partly explain the special features of respiratory control in the perinatal period.

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