title: Prenatal stress is a vulnerability factor for altered morphology and biological activity of microglia cells.
abstract: 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-1β, IL-18, IL-6, TNF-α, 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-1β, IL-18, TNF-α 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.
authors: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences Kraków, Poland.
authors: Joanna
authors: J
authors: Ślusarczyk
authors: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences Kraków, Poland.
authors: Ewa
authors: E
authors: Trojan
authors: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences Kraków, Poland.
authors: Katarzyna
authors: K
authors: Głombik
authors: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences Kraków, Poland.
authors: Bogusława
authors: B
authors: Budziszewska
authors: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences Kraków, Poland.
authors: Marta
authors: M
authors: Kubera
authors: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences Kraków, Poland.
authors: Władysław
authors: W
authors: Lasoń
authors: Department of Pain Pharmacology, Institute of Pharmacology, Polish Academy of Sciences Kraków, Poland.
authors: Katarzyna
authors: K
authors: Popiołek-Barczyk
authors: Department of Pain Pharmacology, Institute of Pharmacology, Polish Academy of Sciences Kraków, Poland.
authors: Joanna
authors: J
authors: Mika
authors: Laboratory of Pharmacology and Brain Biostructure, Institute of Pharmacology, Polish Academy of Sciences Kraków, Poland.
authors: Krzysztof
authors: K
authors: Wędzony
authors: Department of Experimental Neuroendocrinology, Institute of Pharmacology, Polish Academy of Sciences Kraków, Poland.
authors: Agnieszka
authors: A
authors: Basta-Kaim
keywords: chemokines; cytokines; depressive-like behavior; inflammation; microglia; neurotrophic factors; prenatal stress