Release of inhibitory neurotransmitters in response to anoxia in turtle brain

1991 ◽  
Vol 261 (1) ◽  
pp. R32-R37 ◽  
Author(s):  
G. E. Nilsson ◽  
P. L. Lutz

In mammals a massive release of the excitatory neurotransmitter glutamate, occurring within a few minutes of anoxia/ischemia, is thought to be a major mediator of anoxic brain damage. In contrast to the mammalian brain, the turtle brain is exceptionally anoxia tolerant. Using intracerebral microdialysis in turtle brain striatum, we have found a large increase in the extracellular level of the inhibitory neurotransmitter gamma-aminobutyric acid during anoxia, reaching 90 times the normoxic level after 240 min, whereas no substantial release of glutamate occurred. Moreover, the inhibitory neurotransmitters/neuromodulators glycine and taurine also displayed increased extracellular levels during anoxia. Increased extracellular levels of inhibitory amino acids may be one of the hitherto elusive mechanisms that underlie the decreased activity and energy consumption characterizing the anoxic turtle brain.

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Chun-Ping Huang ◽  
Yi-Wen Lin ◽  
Der-Yen Lee ◽  
Ching-Liang Hsieh

Neuropathic pain caused by peripheral tissue injuries to the higher brain regions still has no satisfactory therapy. Disruption of the balance of excitatory and inhibitory neurotransmitters is one of the underlying mechanisms that results in chronic neuropathic pain. Targeting neurotransmitters and related receptors may constitute a novel approach for treating neuropathic pain. We investigated the effects of electroacupuncture (EA) on chronic constriction injury- (CCI-) induced neuropathic pain. The mechanical allodynia and thermal hyperalgesia pain behaviors were relieved by 15 Hz EA but not by 2 and 50 Hz. These phenomena were associated with increasing γ-amino-butyric acid (GABA) receptors in the hippocampus and periaqueductal gray (PAG) but not N-methyl-D-aspartate receptors. Furthermore, excitatory neurotransmitter glutamate was decreased in the hippocampus and inhibitory neurotransmitter GABA was increased in the PAG under treatment with EA. These data provide novel evidence that EA modulates neurotransmitters and related receptors to reduce neuropathic pain in the higher brain regions. This suggests that EA may be a useful therapy option for treating neuropathic pain.


2020 ◽  
Author(s):  
Dania Abuleil ◽  
Daphne McCulloch ◽  
Benjamin Thompson

AbstractNeuromodulation of the primary visual cortex using anodal transcranial direct current stimulation (a-tDCS) can alter visual perception and enhance neuroplasticity. However, the mechanisms that underpin these effects are currently unknown. When applied to the motor cortex, a-tDCS reduces the concentration of the inhibitory neurotransmitter gamma aminobutyric acid (GABA), an effect that has been linked to increased neuroplasticity. The aim of this study was to assess whether a-tDCS also reduces GABA-mediated inhibition when applied to the human visual cortex. Changes in visual cortex inhibition were measured using the mixed percept duration in binocular rivalry. Binocular rivalry mixed percept duration has recently been advocated as a direct and sensitive measure of visual cortex inhibition whereby GABA agonists decrease mixed percept durations and agonists of the excitatory neurotransmitter acetylcholine increase them. Our hypothesis was that visual cortex a-tDCS would increase mixed percept duration by reducing GABA-mediated inhibition and increasing cortical excitation. In addition, we measured the effect of continuous theta-burst transcranial magnetic stimulation (cTBS) of the visual cortex on binocular rivalry dynamics. When applied to the motor or visual cortex, cTBS increases GABA concentration and we therefore hypothesized that visual cortex cTBS would decrease the mixed percept duration. Binocular rivalry dynamics were recorded before and after active and sham a-tDCS (N=15) or cTBS (N=15). Contrary to our hypotheses, a-tDCS had no effect, whereas cTBS significantly increased mixed percepts during rivalry. These results suggest that the neurochemical mechanisms of a-tDCS may differ between the motor and visual cortices.


PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0239349
Author(s):  
Dania Abuleil ◽  
Daphne McCulloch ◽  
Benjamin Thompson

Neuromodulation of the primary visual cortex using anodal transcranial direct current stimulation (a-tDCS) can alter visual perception and enhance neuroplasticity. However, the mechanisms that underpin these effects are currently unknown. When applied to the motor cortex, a-tDCS reduces the concentration of the inhibitory neurotransmitter gamma aminobutyric acid (GABA), an effect that has been linked to increased neuroplasticity. The aim of this study was to assess whether a-tDCS also reduces GABA-mediated inhibition when applied to the human visual cortex. Changes in visual cortex inhibition were measured using the mixed percept duration in binocular rivalry. Binocular rivalry mixed percept duration has recently been advocated as a direct and sensitive measure of visual cortex inhibition whereby GABA agonists decrease mixed percept durations and agonists of the excitatory neurotransmitter acetylcholine (ACH) increase them. Our hypothesis was that visual cortex a-tDCS would increase mixed percept duration by reducing GABA-mediated inhibition and increasing cortical excitation. In addition, we measured the effect of continuous theta-burst transcranial magnetic stimulation (cTBS) of the visual cortex on binocular rivalry dynamics. When applied to the motor or visual cortex, cTBS increases GABA concentration and we therefore hypothesized that visual cortex cTBS would decrease the mixed percept duration. Binocular rivalry dynamics were recorded before and after active and sham a-tDCS (N = 15) or cTBS (N = 15). Contrary to our hypotheses, a-tDCS had no effect, whereas cTBS increased mixed percepts during rivalry. These results suggest that the neurochemical mechanisms of a-tDCS may differ between the motor and visual cortices.


2001 ◽  
Vol 79 (12) ◽  
pp. 977-984 ◽  
Author(s):  
Yuewen Gong ◽  
Manna Zhang ◽  
Li Cui ◽  
Gerald Y Minuk

Gamma-aminobutyric acid (GABA) is the predominant inhibitory neurotransmitter in the mammalian brain. Although initially thought to be confined to the central nervous system, GABAergic activity has also been described in other tissues throughout the body. In the present study, we report the cloning and localization of human GABA transporter cDNA and document its expression in various human tissues. A human liver cDNA library was initially screened by a 32P-labeled murine brain GABA transporter 3 (GAT-3) cDNA probe, and full-length cDNA was cloned by employing Marathon-Ready(tm) human kidney cDNA. The human GABA transporter cDNA encoded a 569 amino acid hydrophobic protein with 12 transmembrane domains (TMs). Search of published sequences revealed high homology with rat GAT-2, murine GAT-3 cDNA, human solute carrier family 6 member 13 (SLC6A13), and a human peripheral betaine/GABA transporter. Northern blot analyses demonstrated that the human GABA transporter is expressed strongly in the kidney and to a lesser extent in the liver and brain. The sequence was well matched with human chromosome 12p13.3, suggesting the human GABA transporter contains 14 exons. The above findings confirm the existence of and further characterize a specific GABA transporter in human tissues.Key words: sequence, chromosome, GABA, GABA transporter.


Author(s):  
Shutian Zhang

Background: Hypertension is a cardiovascular syndrome with the highest morbidity and mortality worldwide. Hypertension caused by various stress factors is called stress-induced hypertension (SIH). The rostral ventrolateral medulla (RVLM) "neuroinflammatory-sympathetic overactivation" is involved in SIH formation. Melatonin has anti-inflammatory, anti-oxidant and blood pressure lowering effects. The present study is to explore the antihypertensive effects and mechanism of central melatonin which based on microglia derived neuroinflammation. Methods: Stress-induced hypertension (SIH) was induced by electric foot-shock stressors with noise interventions in rats. Melatonin (0.01,0.1,1 mmol/L) was administered to RVLM and then blood pressure (BP) and serum norepinephrine (NE) were monitored to reflect sympathetic vasomotor activity in SIH rats. Excitatory neurotransmitter (Glutamate) and inhibitory neurotransmitter [γ-aminobutyric acid (GABA)] were measured using ELISA kits. Markers of microglia M1 polarization (CD86) and pro-inflammatory cytokines (PICs (IL-1β, TNF-α)) expression in the RVLM were measured by RT-qPCR. Results: (1) Stress-induced increase in blood pressure and serum NE concentration; RVLM microinjection melatonin attenuated the elevation of blood pressure and increase of plasma NE in SIH rats in a dose-dependent manner. (2) The expression of CD86, PICs (IL-1β, TNF-α) and c-fos were increased in SIH rats; RVLM injection melatonin attenuated RVLM neuroinflammation and its effect is concentration-dependent. (3). Stress-induced increase in glutamate concentration in RVLM; RVLM injection melatonin reduced glutamate level and increased GABA level in SIH rats in a concentration-dependent manner. Conclusion: RVLM injection of melatonin inhibits M1 polarization and has anti-hypertensive effects. Melatonin reduces M1 polarization in microglia might be a novel target and a new strategy for anti-stress induced-hypertension.


2020 ◽  
Author(s):  
Yiwen Cai ◽  
Yingying Tang ◽  
Jijun Wang ◽  
Qinhui Fu ◽  
Min Hang Gan ◽  
...  

Abstract Background: There is evidence suggesting that an imbalance between the levels of the excitatory neurotransmitter, glutamate, and inhibitory neurotransmitter, gamma aminobutyric acid (GABA), leads to migraine attacks; however, the pathophysiology and specific diagnostic markers remain unknown. Methods: Twenty-one migraine patients (18 female, 3 male, mean age=40.63 14.23years) and 11 healthy controls (9 female, 2 male, mean age=39.78 15.31 years) were included in this study. We used 1H-MRS at 3 Tesla with voxels-of-interest located in the bilateral thalamus and subgenual anterior cingulate cortex (SG ACC) to quantify the GABA and GLX (glutamate-glutamine complex) concentrations measured via the Mescher-Garwood point-resolved spectroscopy (MEGA-PRESS) sequence in migraineurs and healthy controls. Result: Statistical analyses revealed significantly decreased GLX/NAA (N-acetylaspartate) in the right thalamus of migraine patients compared to healthy controls. However, we found no group differences in GABA levels in the SG ACC and bilateral thalamus.Conclusion: The right thalamus may be involved in the pain modulation process of migraineurs through changes in the GLX levels. Decreased GLX levels within the right thalamus might be associated with the disruption of "excitation-inhibition" homeostasis in migraine.Trial registration: ClinicalTrials.gov, NCT02580968. Registered 30 October 2015, https://clinicaltrials.gov/ct2/show/study/NCT02580968


Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 530
Author(s):  
Oliviero Bruni ◽  
Luigi Ferini-Strambi ◽  
Elena Giacomoni ◽  
Paolo Pellegrino

Sleep is an essential component of physical and emotional well-being, and lack, or disruption, of sleep due to insomnia is a highly prevalent problem. The interest in complementary and alternative medicines for treating or preventing insomnia has increased recently. Centuries-old herbal treatments, popular for their safety and effectiveness, include valerian, passionflower, lemon balm, lavender, and Californian poppy. These herbal medicines have been shown to reduce sleep latency and increase subjective and objective measures of sleep quality. Research into their molecular components revealed that their sedative and sleep-promoting properties rely on interactions with various neurotransmitter systems in the brain. Gamma-aminobutyric acid (GABA) is an inhibitory neurotransmitter that plays a major role in controlling different vigilance states. GABA receptors are the targets of many pharmacological treatments for insomnia, such as benzodiazepines. Here, we perform a systematic analysis of studies assessing the mechanisms of action of various herbal medicines on different subtypes of GABA receptors in the context of sleep control. Currently available evidence suggests that herbal extracts may exert some of their hypnotic and anxiolytic activity through interacting with GABA receptors and modulating GABAergic signaling in the brain, but their mechanism of action in the treatment of insomnia is not completely understood.


2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Pengkai Wang ◽  
Yini Dong ◽  
Liming Zhu ◽  
Zhaodong Hao ◽  
LingFeng Hu ◽  
...  

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.


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