Journal
NEUROPHARMACOLOGY
Volume 160, Issue -, Pages -Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2019.107776
Keywords
Interleukin-1 beta (IL-1 beta); Glial fibrillary acidic protein (GFAP); gamma-aminobutyric acid (GABA); L-alpha-aminoadipate (L-AAA); 5-Nitro-2-(3-phenylpropylamino) benzoicacid (NPPB); Anxiety
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Funding
- National Research Foundation of Korea (NRF) - Korean government [NRF-2016M3C7A1905384, NRF-2018R1A6A3A01012989]
- Kyung Hee University [KHU-20191211]
- National Research Foundation of Korea [2016M3C7A1905384] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Recent studies have shown that not only neurons but astrocytes contain a considerable amount of gamma-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-1 beta (IL-1 beta), 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-alpha-aminoadipate (L-AAA) reduced anxiety-like behaviors and the GFAP expression in the PVN. Intraparaventricular nucleus (iPVN) infusion of IL-1 beta 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-1 beta-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.
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