Prenatal inflammation impairs adult neurogenesis and memory related behavior through persistent hippocampal TGFb1 downregulation

• Published in: Brain, behavior, and immunity Vol. 24; no. 8; pp. 1301 - 1309
• Main Authors: Graciarena, Mariana, Depino, Amaicha M, Pitossi, Fernando J
• Format: Journal Article
• Language: English
• Published: 01.11.2010
• Subjects: Brain
• ISSN: 0889-1591
• DOI: 10.1016/j.bbi.2010.06.005

a-[ordm Prenatal LPS administration decreases adult neurogenesis in the dentate gyrus (DG). a-[ordm Prenatal LPS treatment induces persistent microglial activation in the adult DG. a-[ordm Prenatal LPS causes specific TGFb1 downregulation in the adult hippocampus. a-[ordm Prenatal LPS impairs adult performance in the Novel Object Recognition (NOR) test. a-[ordm Hippocampal TGFb1 overexpression restores levels of adult neurogenesis and NOR performance. Prenatal exposure to inflammatory stimuli is known to influence adult brain function. In addition, adult hippocampal neurogenesis is impaired by a local pro-inflammatory microenvironment. On this basis, we hypothesized that a pro-inflammatory insult during gestation would have negative effects on adult neurogenesis in the offspring. Pregnant Wistar rats received subcutaneous injections of lipopolysaccharide (LPS; 0.5mg/kg) or saline every other day from gestational day 14 to 20. The adult offspring prenatally treated with LPS showed a decrease in the proliferating cells and the newborn neurons of the dentate gyrus. Furthermore, prenatal LPS treatment impaired performance in the neurogenesis-dependent novel object recognition test. Maternal care was impaired by prenatal LPS administration but did not contribute to the effects of prenatal LPS on adult neurogenesis. Persistent microglial activation and downregulated expression of transforming growth factor beta-1 (TGFb1) occurred specifically in the adult hippocampus of animals treated prenatally with LPS. Importantly, chronic hippocampal TGFb1 overexpression restored neurogenesis as well as recognition memory performance to control levels. These findings demonstrate that prenatal inflammation triggered by LPS impairs adult neurogenesis and recognition memory. Furthermore, we provide a model of reduced adult neurogenesis with long-lasting defined alterations in the neurogenic niche. Finally, we show that the expression of a single cytokine (TGFb1) in the hippocampus can restore adult neurogenesis and its related behavior, highlighting the role of TGFb1 in these processes.