PMID- 31513788 OWN - NLM STAT- MEDLINE DCOM- 20200708 LR - 20200708 IS - 1873-7064 (Electronic) IS - 0028-3908 (Linking) VI - 160 DP - 2019 Dec 1 TI - Role of astrocytic GABAergic system on inflammatory cytokine-induced anxiety-like behavior. PG - 107776 LID - S0028-3908(18)30687-7 [pii] LID - 10.1016/j.neuropharm.2019.107776 [doi] AB - 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-1beta (IL-1beta), 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-1beta 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-1beta-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. CI - Copyright (c) 2019. Published by Elsevier Ltd. FAU - Shim, Hyun Soo AU - Shim HS AD - Department of Physiology, College of Medicine, Kyung Hee University, 1 Hoegi-dong, Dongys0daemun-gu, Seoul, 02447, South Korea; Center for Neuroscience, Brain Science Institute of Science and Technology (KIST), Seoul, 02792, South Korea. FAU - Park, Hyun Jung AU - Park HJ AD - Department of Physiology, College of Medicine, Kyung Hee University, 1 Hoegi-dong, Dongys0daemun-gu, Seoul, 02447, South Korea; Department of Food Science and Biotechnology, Kyonggi University, 154-42, Gwanggyosan-ro, Youngtong-gu, Suwon, Gyeonggi, 16227, South Korea. FAU - Woo, Junsung AU - Woo J AD - Center for Neuroscience, Brain Science Institute of Science and Technology (KIST), Seoul, 02792, South Korea. FAU - Lee, C Justin AU - Lee CJ AD - Center for Neuroscience, Brain Science Institute of Science and Technology (KIST), Seoul, 02792, South Korea. FAU - Shim, Insop AU - Shim I AD - Department of Physiology, College of Medicine, Kyung Hee University, 1 Hoegi-dong, Dongys0daemun-gu, Seoul, 02447, South Korea. Electronic address: ishim@khu.ac.kr. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190909 PL - England TA - Neuropharmacology JT - Neuropharmacology JID - 0236217 RN - 0 (Cytokines) RN - 0 (Glial Fibrillary Acidic Protein) RN - 0 (IL1B protein, rat) RN - 0 (Interleukin-1beta) RN - 0 (Nitrobenzoates) RN - 3A35O9G3YZ (5-nitro-2-(3-phenylpropylamino)benzoic acid) RN - 56-12-2 (gamma-Aminobutyric Acid) SB - IM MH - Animals MH - Anxiety/*chemically induced/drug therapy MH - Astrocytes/*metabolism MH - Behavior, Animal MH - Cytokines/metabolism MH - GABAergic Neurons/*metabolism MH - Glial Fibrillary Acidic Protein/metabolism MH - Inflammation/metabolism MH - Infusions, Intraventricular MH - Interleukin-1beta/*administration & dosage/adverse effects MH - Male MH - Nitrobenzoates/therapeutic use MH - Paraventricular Hypothalamic Nucleus/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - gamma-Aminobutyric Acid/adverse effects/metabolism OTO - NOTNLM OT - 5-Nitro-2-(3-phenylpropylamino) benzoicacid (NPPB) OT - Anxiety OT - Glial fibrillary acidic protein (GFAP) OT - Interleukin-1beta (IL-1beta) OT - l-alpha-aminoadipate (L-AAA) OT - gamma-aminobutyric acid (GABA) EDAT- 2019/09/13 06:00 MHDA- 2020/07/09 06:00 CRDT- 2019/09/13 06:00 PHST- 2018/09/19 00:00 [received] PHST- 2019/09/07 00:00 [revised] PHST- 2019/09/08 00:00 [accepted] PHST- 2019/09/13 06:00 [pubmed] PHST- 2020/07/09 06:00 [medline] PHST- 2019/09/13 06:00 [entrez] AID - S0028-3908(18)30687-7 [pii] AID - 10.1016/j.neuropharm.2019.107776 [doi] PST - ppublish SO - Neuropharmacology. 2019 Dec 1;160:107776. doi: 10.1016/j.neuropharm.2019.107776. Epub 2019 Sep 9.