PMID- 25814933 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20150327 LR - 20200930 IS - 1662-5102 (Print) IS - 1662-5102 (Electronic) IS - 1662-5102 (Linking) VI - 9 DP - 2015 TI - Prenatal stress is a vulnerability factor for altered morphology and biological activity of microglia cells. PG - 82 LID - 10.3389/fncel.2015.00082 [doi] LID - 82 AB - Several lines of evidence suggest that the dysregulation of the immune system is an important factor in the development of depression. Microglia are the resident macrophages of the central nervous system and a key player in innate immunity of the brain. We hypothesized that prenatal stress (an animal model of depression) as a priming factor could affect microglial cells and might lead to depressive-like disturbances in adult male rat offspring. We investigated the behavioral changes (sucrose preference test, Porsolt test), the expression of C1q and CD40 mRNA and the level of microglia (Iba1 positive) in 3-month-old control and prenatally stressed male offspring rats. In addition, we characterized the morphological and biochemical parameters of potentially harmful (NO, iNOS, IL-1beta, IL-18, IL-6, TNF-alpha, CCL2, CXCL12, CCR2, CXCR4) and beneficial (insulin-like growth factor-1 (IGF-1), brain derived neurotrophic factor (BDNF)) phenotypes in cultures of microglia obtained from the cortices of 1-2 days old control and prenatally stressed pups. The adult prenatally stressed rats showed behavioral (anhedonic- and depression-like) disturbances, enhanced expression of microglial activation markers and an increased number of Iba1-immunopositive cells in the hippocampus and frontal cortex. The morphology of glia was altered in cultures from prenatally stressed rats, as demonstrated by immunofluorescence microscopy. Moreover, in these cultures, we observed enhanced expression of CD40 and MHC II and release of pro-inflammatory cytokines, including IL-1beta, IL-18, TNF-alpha and IL-6. Prenatal stress significantly up-regulated levels of the chemokines CCL2, CXCL12 and altered expression of their receptors, CCR2 and CXCR4 while IGF-1 production was suppressed in cultures of microglia from prenatally stressed rats. Our results suggest that prenatal stress may lead to excessive microglia activation and contribute to the behavioral changes observed in depression in adulthood. FAU - Slusarczyk, Joanna AU - Slusarczyk J AD - Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences Krakow, Poland. FAU - Trojan, Ewa AU - Trojan E AD - Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences Krakow, Poland. FAU - Glombik, Katarzyna AU - Glombik K AD - Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences Krakow, Poland. FAU - Budziszewska, Boguslawa AU - Budziszewska B AD - Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences Krakow, Poland. FAU - Kubera, Marta AU - Kubera M AD - Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences Krakow, Poland. FAU - Lason, Wladyslaw AU - Lason W AD - Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences Krakow, Poland. FAU - Popiolek-Barczyk, Katarzyna AU - Popiolek-Barczyk K AD - Department of Pain Pharmacology, Institute of Pharmacology, Polish Academy of Sciences Krakow, Poland. FAU - Mika, Joanna AU - Mika J AD - Department of Pain Pharmacology, Institute of Pharmacology, Polish Academy of Sciences Krakow, Poland. FAU - Wedzony, Krzysztof AU - Wedzony K AD - Laboratory of Pharmacology and Brain Biostructure, Institute of Pharmacology, Polish Academy of Sciences Krakow, Poland. FAU - Basta-Kaim, Agnieszka AU - Basta-Kaim A AD - Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences Krakow, Poland. LA - eng PT - Journal Article DEP - 20150312 PL - Switzerland TA - Front Cell Neurosci JT - Frontiers in cellular neuroscience JID - 101477935 PMC - PMC4357262 OTO - NOTNLM OT - chemokines OT - cytokines OT - depressive-like behavior OT - inflammation OT - microglia OT - neurotrophic factors OT - prenatal stress EDAT- 2015/03/31 06:00 MHDA- 2015/03/31 06:01 PMCR- 2015/01/01 CRDT- 2015/03/28 06:00 PHST- 2014/12/12 00:00 [received] PHST- 2015/02/23 00:00 [accepted] PHST- 2015/03/28 06:00 [entrez] PHST- 2015/03/31 06:00 [pubmed] PHST- 2015/03/31 06:01 [medline] PHST- 2015/01/01 00:00 [pmc-release] AID - 10.3389/fncel.2015.00082 [doi] PST - epublish SO - Front Cell Neurosci. 2015 Mar 12;9:82. doi: 10.3389/fncel.2015.00082. eCollection 2015.