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Updated: May 20, 2026
Continuous Video Electroencephalogram during Hypoxia-Ischemia in Neonatal Mice
Published on: June 11, 2020
The dynamics of changes in hippocampal GABAergic system in rats exposed to early-life hypoxia-induced seizures
L Yatsenko1, N Pozdnyakova, M Dudarenko
1Department of Neurochemistry, Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Leontovich Str. 9, Kyiv 01601, Ukraine.
Insights
Early-life hypoxia-evoked seizures (H/S) alter GABA release and uptake in rat hippocampus. Enhanced GABA(B) receptor auto-inhibition contributes to hyperexcitability after H/S.
Area of Science:
- Neuroscience
- Neurophysiology
- Developmental Neuroscience
Background:
- Hypoxia-evoked seizures (H/S) in early life cause lasting neurological deficits.
- The GABAergic system, crucial for inhibitory neurotransmission, is implicated in seizure disorders.
Purpose of the Study:
- To investigate the long-term effects of early-life H/S on GABA release, uptake, and GABA(B) receptor regulation in the rat hippocampus.
- To understand how H/S impacts age-dependent changes in the GABAergic system.
Main Methods:
- Exocytotic GABA release, GABA uptake rates, and GABA(B) receptor-mediated auto-inhibition were measured in hippocampal synaptosomes from rats at 2, 4, and 8 weeks post-H/S.
- Radioactive [(3)H]GABA was used to quantify release and uptake.
- GABA(B) receptor agonists (±)-baclofen and SKF 97541 were employed.
Main Results:
- Exocytotic GABA release was elevated in H/S rats, peaking at 2 weeks post-injury.
- GABA uptake rates decreased with age, with a more pronounced decline in H/S rats.
- GABA(B) receptor-mediated auto-inhibition of GABA release was significantly enhanced in adult H/S rats compared to controls.
Conclusions:
- Early-life H/S disrupts age-dependent maturation of the hippocampal GABAergic system.
- Enhanced presynaptic GABA(B) receptor auto-inhibition following H/S may contribute to reduced postsynaptic inhibition and subsequent hyperexcitability.
Abstract:
Hypoxia-evoked seizures (H/S) early in life lead to multiple chronic neurological deficits. Here, we present the results of studying GABA release and uptake in hippocampal axon terminals of rats exposed to H/S at 10-12 days of age. We characterized (i) exocytotic release of GABA; (ii) the initial rate of GABA uptake; (iii) the regulation of GABA release by presynaptic GABA(B) receptors. Rats were used for experiments 2, 4 and 8 weeks after H/S. We found that exocytotic [(3)H]GABA release was higher in rats exposed to H/S, and a maximal difference in the release was observed between the control and experimental rats tested 2 weeks after H/S. In contrast, the initial rate of GABA uptake decreased with age, and this tendency was more pronounced in rats exposed to H/S. Using (±)-baclofen and SKF 97541 as agonists of GABA(B) receptor, we revealed that a significant difference in the auto-inhibition of exocytotic [(3)H]GABA release was detected only between the control and experimental adult rats (8 weeks after hypoxia). The inhibitory effect dropped dramatically in the control adults, but only slightly decreased in adult rats exposed to H/S, thus becoming threefold more potent after hypoxic injury. Together, the results show that H/S affects the dynamics of age-dependent changes in the GABAergic system, and that the enhanced GABA(B) receptor-mediated auto-inhibition can be an important factor in weakening the postsynaptic inhibition and in the development of hyperexcitability in rats exposed to H/S.
