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Effects of interleukin-1beta on hippocampal glutamate and GABA releases associated with Ca2+-induced Ca2+ releasing
Gang Zhu1, Motohiro Okada, Shukuko Yoshida
1Department of Neuropsychiatry, Hirosaki University School of Medicine, Hirosaki 036-8562, Japan.
Insights
Interleukin-1beta (IL-1beta) affects neurotransmitter release in the hippocampus. This cytokine disrupts the balance between glutamate and GABA, potentially contributing to seizures.
Area of Science:
- Neuroscience
- Neuroinflammation
- Molecular Biology
Background:
- Interleukin-1beta (IL-1beta) is implicated in febrile and epileptic seizures.
- Understanding IL-1beta's role in neurotransmission is crucial for seizure research.
Purpose of the Study:
- To investigate the effects of IL-1beta on calcium-associated glutamate and GABA release in the mouse hippocampus.
- To elucidate the mechanisms underlying IL-1beta's modulation of basal and evoked neurotransmitter release.
Main Methods:
- Electrophysiological recordings in mouse hippocampal slices.
- Measurement of basal and potassium-evoked glutamate and GABA release.
- Pharmacological manipulation of calcium influx and calcium-induced calcium release (CICR) pathways, including ryanodine receptors (RyR) and inositol 1,4,5-trisphosphate receptors (IP3R).
Main Results:
- IL-1beta enhanced basal glutamate and GABA release via Ca2+ influx and RyR-sensitive CICR.
- IL-1beta reduced K+-evoked glutamate and GABA release, involving both RyR- and IP3R-sensitive CICR.
- During hyperexcitability, IL-1beta's effect on GABA release was primarily modulated by Ca2+ influx and RyR-sensitive CICR.
Conclusions:
- Hyperactivation of IL-1beta disrupts glutamatergic and GABAergic transmission.
- This imbalance occurs through a toxic overload response involving Ca2+ influx and CICR.
- IL-1beta's actions contribute to the generation of seizures by altering neuronal excitability.
Abstract:
Recent clinical and basic studies have demonstrated that hyperactivation of interleukin-1beta (IL-1beta) plays important roles in generation of febrile and epileptic seizures. To clarify this mechanism, the present study determined the effects of IL-1beta on Ca2+-associated releases of glutamate and GABA in mouse hippocampus. Both basal and K+-evoked GABA releases were regulated by Ca2+ influx and Ca2+-induced Ca2+ releasing system (CICR). The K+-evoked glutamate release was also regulated by Ca2+ influx and CICR, whereas basal glutamate release was not affected by them. IL-1beta increased basal releases of glutamate and GABA depending on the activation of Ca2+ influx and ryanodine receptor (RyR)-sensitive CICR, but reduced K+-evoked releases depending on Ca2+ influx, RyR-sensitive and inositol 1,4,5-trisphosphate receptor (IP3R)-sensitive CICRs. During neuronal hyperexcitability, the effect of IL-1beta on GABA release was more predominantly modulated by Ca2+ influx and RyR-sensitive CICR than that on glutamate. These results indicate that hyperactivation of IL-1beta leads to imbalance between glutamatergic and GABAergic transmission via toxic overload response of Ca2+ influx and CICR.
