Role of astrocytic GABAergic system on inflammatory cytokine-induced anxiety-like behavior. (1st December 2019)

• Record Type: Journal Article
• Authors: Shim, Hyun Soo; Park, Hyun Jung; Woo, Junsung; Lee, C. Justin; Shim, Insop
• Is Part Of: Neuropharmacology. Volume 160(2019)
• Publication Date: 2019-12-01
• Subjects: Interleukin-1β (IL-1β) -- Glial fibrillary acidic protein (GFAP) -- γ-aminobutyric acid (GABA) -- l-α-aminoadipate (L-AAA) -- 5-Nitro-2-(3-phenylpropylamino) benzoicacid (NPPB) -- Anxiety; Neuropsychopharmacology -- Periodicals; Autonomic Agents -- Periodicals; Neuropsychopharmacologie -- Périodiques; Neuropsychopharmacology; Periodicals; Electronic journals; 615.78
• DOI: 10.1016/j.neuropharm.2019.107776
• Languages: English
• ISSNs: 0028-3908

Abstract

Abstract: Recent studies have shown that not only neurons but astrocytes contain a considerable amount of γ-aminobutyric acid (GABA), which can be released and activate the receptors responsive to GABA. The purpose of this study is to test whether gliotransmitters from astrocytes may play a role in etiology of anxiety symptoms. Intracerebroventricular (i.c.v.) infusion of interleukin-1β (IL-1β), one of potent inflammatory cytokines, induced anxiety-like behaviors and activated the glial fibrillary acidic protein (GFAP) in the paraventricular nucleus (PVN) of the hypothalamus. Pretreatment with astrocytes toxin, l -α-aminoadipate (L-AAA) reduced anxiety-like behaviors and the GFAP expression in the PVN. Intraparaventricular nucleus (iPVN) infusion of IL-1β produced markedly anxiety-like behaviors and increased release of GABA from astrocytes. However, treatment of glial cell inhibitor, L-AAA or blocker of Bestrophin-1 (Best1), 5-Nitro-2-(3-phenylpropylamino) benzoic acid (NPPB) markedly inactivated astrocytes and also reduced the anxiety-like behaviors. Treatment of L-AAA or NPPB decreased IL-1β-induced gliotransmitter GABA release measured by in vivo microdialysis. These results suggest that selective inhibition of astrocytes or astocytic GABA release in the PVN may serve as an effective therapeutic strategy for treating anxiety and affective disorders. Highlights: IL-1β induces anxiety-like behaviors. Astrocyte produces and releases GABA in IL-1β induced anxiety-like animal model. L-AAA or NPPB administration normalized metabolism of neurotransmitter and astrocyte activation. L-AAA or NPPB may serve an effective therapeutic strategy for treating anxietyresponses.