GABA receptor inhibition and severe hypoxia induce a paroxysmal depolarization shift in goldfish neurons

Hossein-Javaheri, Nariman; Buck, Leslie T.

doi:10.1152/jn.00149.2020

Cited by 10 publications

(7 citation statements)

References 54 publications

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“…It is known that rising water temperatures can reduce the dissolved oxygen (DO) level and increase the oxygen for aquatic animals, as well as elevate the carbon dioxide (CO 2 ) levels in water (hypercapnia) which causes serious threat to water breathers like fish [ 22 , 42 , 43 ]. GABAergic signaling is one of the major pathways that contributes to neuronal survival during anoxia stress by suppressing cellular excitability [ 44 ]. Without the protective effects of GABA, brain neurons are incapable of tolerating anoxia and undergo excitotoxicity in terms of excessive glutamate exposure and disruption of the glutamate/GABA ratio that causes cellular swelling, irreversible neuronal injury and eventually cell death [ 44 , 45 ].…”

Section: Discussionmentioning

confidence: 99%

Interactive Effect of Dietary Gamma-Aminobutyric Acid (GABA) and Water Temperature on Growth Performance, Blood Plasma Indices, Heat Shock Proteins and GABAergic Gene Expression in Juvenile Olive Flounder Paralichthys olivaceus

et al. 2023

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Gamma-aminobutyric acid (GABA) is an important inhibitory neurotransmitter in the central nervous system of living organisms and has the ability to reduce the magnitude of stress in humans and animals. In this study, we evaluated the supplemental effects of GABA on normal and high water temperature based on growth, blood plasma composition as well as heat shock proteins and GABA-related gene expression in juvenile olive flounder. For this, a 2 × 2 factorial design of experiment was employed to investigate the dietary effects of GABA at 0 mg/kg of diet (GABA0 diet) and 200 mg/kg of diet (GABA200 diet) in water temperatures of 20 ± 1 °C (normal temperature) and 27 ± 1 °C (high temperature) for 28 days. A total of 180 fish with an average initial weight of 40.1 ± 0.4 g (mean ± SD) were distributed into 12 tanks, of which, each tank contained 15 fish based on the 4 dietary treatment groups in triplicate. At the end of the feeding trial, the results demonstrated that both temperature and GABA had significant effects on the growth performance of the fish. However, fish fed the GABA200 diet had a significantly higher final body weight, weight gain and specific growth rate as well as a significantly lower feed conversion ratio than the fish fed the GABA0 diet at the high water temperature. A significant interactive effect of water temperature and GABA was observed on the growth performance of olive flounder based on the two-way analysis of variance. The plasma GABA levels in fish were increased in a dose-dependent manner at normal or high water temperatures, whereas cortisol and glucose levels were decreased in fish fed GABA-supplemented diets under temperature stress. The GABA-related mRNA expression in the brains of the fish such as GABA type A receptor-associated protein (Gabarap), GABA type B receptor 1 (Gabbr1) and glutamate decarboxylase 1 (Gad1) were not significantly affected by GABA-supplemented diets under normal or temperature stressed conditions. On the other hand, the mRNA expression of heat shock proteins (hsp) in the livers of the fish, such as hsp70 and hsp90, were unchanged in fish fed the GABA diets compared to the control diet at the high water temperature. Collectively, the present study showed that dietary supplementation with GABA could enhance growth performance, and improve the feed utilization, plasma biochemical parameters and heat shock proteins and GABA-related gene expression under the stress of high water temperatures in juvenile olive flounder.

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Section: Discussionmentioning

confidence: 99%

Interactive Effect of Dietary Gamma-Aminobutyric Acid (GABA) and Water Temperature on Growth Performance, Blood Plasma Indices, Heat Shock Proteins and GABAergic Gene Expression in Juvenile Olive Flounder Paralichthys olivaceus

et al. 2023

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“…For hypoxia due to stroke, a mechanism for increasing neural inhibition in response to the hypoxic effects could be beneficial, as discussed in the previous section. An important research question is to understand the physiological mechanisms that could connect hypoxia to increased neural inhibition (56-58).…”

Section: Discussionmentioning

confidence: 99%

Thermodynamic limitations on brain oxygen metabolism: physiological implications

Buxton

2023

Preprint

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A recent hypothesis is that maintaining the brain tissue ratio of O2 to CO2 is critical for preserving the entropy increase available from oxidative metabolism of glucose, with a fall of that available entropy leading to a reduction of the phosphorylation potential and impairment of brain energy metabolism. The hypothesis suggests that physiological responses under different conditions can be understood as preserving tissue O2/CO2. To test this idea, a mathematical model of O2 and CO2 transport was used to calculate how well different physiological responses maintain tissue O2/CO2, showing good agreement with reported experimental measurements for increased neural activity, hypercapnia and hypoxia. The results highlight the importance of thinking about brain blood flow as a way to modulate tissue O2/CO2, rather than simply in terms of O2 delivery to the capillary bed. The hypoxia modeling focused on humans at high altitude, including acclimatized lowlanders and adapted populations, with a primary finding that decreasing CO2 by increasing ventilation rate is much more effective for preserving tissue O2/CO2 than increasing blood hemoglobin content. The modeling provides a new framework and perspective for understanding how blood flow and other physiological factors support energy metabolism in the brain under a wide range of conditions.

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“…Additional molecular and physiological mechanisms contributing to the reduction in (oxygen-dependent) ATP-demand as well as the facilitation of oxygen delivery have been described in the brains of goldfish and crucian carp exposed to severe hypoxia and/or anoxia 28 . A reduction in excitatory glutamate signaling and induction of inhibitory GABA-signaling have been reported in both species 29 , 30 . Brain glycogen stores reveal seasonal patterns in crucian carp supporting a crucial role as a limiting energy source to promote anaerobic metabolism 31 , 32 .…”

Section: Discussionmentioning

confidence: 91%

“…Na + /K + -ATPase is crucially involved in maintaining neuronal membrane potential, and ‘channel arrest’ has been linked to a reduction in brain energy demands as well as hypoxia tolerance. Moreover, GABAergic signalling supresses neuronal signalling and is necessary to avoid neuronal excitotoxicity, a consequence of channel arrest in severe hypoxia 30 . These ATP-conserving mechanisms and/or prioritization of oxygen delivery to the brain appear to be highly effective in 4WH brain acclimated to chronic hypoxia, given that it is the only tissue and time point in our study in which the hypoxia marker egln3 is not induced.…”

Section: Discussionmentioning

confidence: 99%

Epigenetic and post-transcriptional repression support metabolic suppression in chronically hypoxic goldfish

Farhat¹,

Talarico²,

Grégoire³

et al. 2022

Sci Rep

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Goldfish enter a hypometabolic state to survive chronic hypoxia. We recently described tissue-specific contributions of membrane lipid composition remodeling and mitochondrial function to metabolic suppression across different goldfish tissues. However, the molecular and especially epigenetic foundations of hypoxia tolerance in goldfish under metabolic suppression are not well understood. Here we show that components of the molecular oxygen-sensing machinery are robustly activated across tissues irrespective of hypoxia duration. Induction of gene expression of enzymes involved in DNA methylation turnover and microRNA biogenesis suggest a role for epigenetic transcriptional and post-transcriptional suppression of gene expression in the hypoxia-acclimated brain. Conversely, mechanistic target of rapamycin-dependent translational machinery activity is not reduced in liver and white muscle, suggesting this pathway does not contribute to lowering cellular energy expenditure. Finally, molecular evidence supports previously reported chronic hypoxia-dependent changes in membrane cholesterol, lipid metabolism and mitochondrial function via changes in transcripts involved in cholesterol biosynthesis, β-oxidation, and mitochondrial fusion in multiple tissues. Overall, this study shows that chronic hypoxia robustly induces expression of oxygen-sensing machinery across tissues, induces repressive transcriptional and post-transcriptional epigenetic marks especially in the chronic hypoxia-acclimated brain and supports a role for membrane remodeling and mitochondrial function and dynamics in promoting metabolic suppression.

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GABA receptor inhibition and severe hypoxia induce a paroxysmal depolarization shift in goldfish neurons

Abstract: This work shows that the combination of anoxia and inhibition of GABA receptors induces seizure-like activities in goldfish telencephalic pyramidal and stellate neurons. Importantly, to prevent seizure-like activity, an intact GABA-mediated inhibitory pathway is required.

Cited by 10 publications

References 54 publications

Interactive Effect of Dietary Gamma-Aminobutyric Acid (GABA) and Water Temperature on Growth Performance, Blood Plasma Indices, Heat Shock Proteins and GABAergic Gene Expression in Juvenile Olive Flounder Paralichthys olivaceus

Interactive Effect of Dietary Gamma-Aminobutyric Acid (GABA) and Water Temperature on Growth Performance, Blood Plasma Indices, Heat Shock Proteins and GABAergic Gene Expression in Juvenile Olive Flounder Paralichthys olivaceus

Thermodynamic limitations on brain oxygen metabolism: physiological implications

Epigenetic and post-transcriptional repression support metabolic suppression in chronically hypoxic goldfish

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