PMID- 30003978 OWN - NLM STAT- MEDLINE DCOM- 20190416 LR - 20190416 IS - 1872-7549 (Electronic) IS - 0166-4328 (Linking) VI - 356 DP - 2019 Jan 1 TI - Minocycline ameliorates depressive behaviors and neuro-immune dysfunction induced by chronic unpredictable mild stress in the rat. PG - 348-357 LID - S0166-4328(18)30395-4 [pii] LID - 10.1016/j.bbr.2018.07.001 [doi] AB - Activated microglia-induced neuroinflammation can stimulate the hypothalamic- pituitary-adrenal (HPA) axis to release glucocorticoids and suppress astrocyte functions, such as reducing neurotrophin production, which occur in depression. However, the balance between M1 (pro-inflammation) and M2 (anti-inflammation) microglial phenotypes and the interaction between these two glial cells are unclear in the depression. Hence, the chronic unpredictable mild stress (CUMS)-induced depression model was chosen to study depression- and anxiety-like behaviors, the concentration of corticosterone and relevant hippocampal cytokines, mRNA and protein expressions of microglial and astrocyte markers. To demonstrate the role of M1 phenotype activation in depression, the effect of microglial inhibitor minocycline on these aspects was also evaluated. Six weeks after CUMS exposure, behaviors were tested. Compared to the control group, CUMS increased serum corticosterone concentration and depression-like behaviors, like anhedonia, helplessness and anxiety. Moreover, CUMS increased microglia M1 marker CD11b expression and tumor necrosis factor (TNF)-alpha, interferon (INF)-gamma, interleukin (IL)-1beta and IL-17 concentrations, but decreased the concentration of M2 cytokines, IL-4, IL-10 and IL-13. Meanwhile, CUMS inhibited the expressions of astrocyte marker glial fibrillary acidic protein (GFAP), brain-derived neurotrophic factor (BDNF) and TrKB. Minocycline (40 mg/kg, 45 days) treatment significantly attenuated CUMS-induced behavioral abnormalities, which were associated with the suppressed M1 response, restored GFAP, BDNF and its receptor expression. In conclusion, CUMS-induced depression- and anxiety-like behavior may result from an imbalance between M1 and M2 and suppressed astrocyte function. Minocycline treatment reversed M1 response, which was associated with behavioral normalization. CI - Copyright (c) 2018 Elsevier B.V. All rights reserved. FAU - Zhang, Cai AU - Zhang C AD - Research Institute for Marine Drug & Nutrition, College of Food Science & Technology, Guangdong Ocean University, Zhanjiang, and Marine Medicine Development Center, Shenzhen Institute, Guangdong Ocean University, Shenzhen, Guangdong, China. FAU - Zhang, Yong-Ping AU - Zhang YP AD - Research Institute for Marine Drug & Nutrition, College of Food Science & Technology, Guangdong Ocean University, Zhanjiang, and Marine Medicine Development Center, Shenzhen Institute, Guangdong Ocean University, Shenzhen, Guangdong, China. FAU - Li, Yu-Yu AU - Li YY AD - Research Institute for Marine Drug & Nutrition, College of Food Science & Technology, Guangdong Ocean University, Zhanjiang, and Marine Medicine Development Center, Shenzhen Institute, Guangdong Ocean University, Shenzhen, Guangdong, China. FAU - Liu, Bai-Ping AU - Liu BP AD - Research Institute for Marine Drug & Nutrition, College of Food Science & Technology, Guangdong Ocean University, Zhanjiang, and Marine Medicine Development Center, Shenzhen Institute, Guangdong Ocean University, Shenzhen, Guangdong, China. FAU - Wang, Hao-Yin AU - Wang HY AD - Research Institute for Marine Drug & Nutrition, College of Food Science & Technology, Guangdong Ocean University, Zhanjiang, and Marine Medicine Development Center, Shenzhen Institute, Guangdong Ocean University, Shenzhen, Guangdong, China. FAU - Li, Kang-Wei AU - Li KW AD - Research Institute for Marine Drug & Nutrition, College of Food Science & Technology, Guangdong Ocean University, Zhanjiang, and Marine Medicine Development Center, Shenzhen Institute, Guangdong Ocean University, Shenzhen, Guangdong, China. FAU - Zhao, Shannon AU - Zhao S AD - American Studies and Ethnicity, University of Southern California, Los Angeles, CA, 90089, USA. FAU - Song, Cai AU - Song C AD - Research Institute for Marine Drug & Nutrition, College of Food Science & Technology, Guangdong Ocean University, Zhanjiang, and Marine Medicine Development Center, Shenzhen Institute, Guangdong Ocean University, Shenzhen, Guangdong, China. Electronic address: cai.song@dal.ca. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180709 PL - Netherlands TA - Behav Brain Res JT - Behavioural brain research JID - 8004872 RN - 0 (Antidepressive Agents) RN - 0 (Brain-Derived Neurotrophic Factor) RN - FYY3R43WGO (Minocycline) SB - IM MH - Animals MH - Antidepressive Agents/*pharmacology MH - Anxiety Disorders/drug therapy MH - Behavior, Animal MH - Brain-Derived Neurotrophic Factor/metabolism MH - Depression/drug therapy/metabolism MH - Disease Models, Animal MH - Female MH - Hypothalamo-Hypophyseal System/drug effects/metabolism MH - Minocycline/*pharmacology MH - Pituitary-Adrenal System/drug effects/metabolism MH - Rats, Sprague-Dawley MH - Stress, Psychological/*drug therapy/metabolism OTO - NOTNLM OT - Behavior OT - Chronic unpredictable mild stress OT - Cytokines OT - Microglial M1 OT - Minocycline OT - Neurotrophins EDAT- 2018/07/14 06:00 MHDA- 2019/04/17 06:00 CRDT- 2018/07/14 06:00 PHST- 2018/03/15 00:00 [received] PHST- 2018/06/12 00:00 [revised] PHST- 2018/07/02 00:00 [accepted] PHST- 2018/07/14 06:00 [pubmed] PHST- 2019/04/17 06:00 [medline] PHST- 2018/07/14 06:00 [entrez] AID - S0166-4328(18)30395-4 [pii] AID - 10.1016/j.bbr.2018.07.001 [doi] PST - ppublish SO - Behav Brain Res. 2019 Jan 1;356:348-357. doi: 10.1016/j.bbr.2018.07.001. Epub 2018 Jul 9.