Role of prenatal LPS on adult neurogenesis

MARIANA GRACIARENA; DANIELA BATTISTA; FERNANDO PITOSSI

San Diego

Congreso; Neuroscience Annual Meeting; 2007

The perinatal stage is characterized by sensitivity to certain stimuli that will be reflected in the adult. Prenatal restraint stress has shown to reduce adult neurogenesis and increase corticosterone, an antiinflammatory and antineurogenic hormone. As it has been reported that prenatal exposure to lipopolysaccharide (LPS), a well known cytokine inducer, provokes long-lasting changes in corticosterone release, we hypothesized that prenatal LPS could also affect adult neurogenesis. To test this hypothesis we injected Wistar pregnant rats subcutaneously with LPS (0,5 mg/kg) at embryonic days 14, 16, 18 and 20, and studied long-term effects of prenatal LPS treatment on adult neurogenesis and corticosterone levels. At postnatal day 60, rats were injected with 50 mg/kg of bromodeoxyuridine (BrdU, intraperitoneal - i.p.) daily for 7 days, and perfused at the 7th day. Neurogenesis and progenitor cell proliferation were assessed by co-labeling of BrdU and neuronal markers (PSA-NCAM or NeuN) and progenitor cell marker (Nestin), respectively. We observed significantly reduced adult neurogenesis levels in prenatally LPS-treated rats, while proliferation and total progenitor cell population remained unchanged. Moreover, microglial activation was observed in prenatally LPS-treated group, suggesting an effect in the local environment. To study whether prenatal LPS treatment resulted in adult increased sensitivity to LPS, we injected LPS (1 mg/kg, ip) in adult rats treated prenatally with LPS or vehicle. Interestingly, adult LPS treatment did not further diminish neurogenesis levels of prenatally LPS-treated rats. Basal corticosterone levels were equal in rats prenatally treated with LPS or Saline, but adult LPS injection caused an exacerbated corticosterone increase in the prenatally LPS-treated group.   We conclude that prenatal LPS challenge impairs adult neurogenesis, particularly neuronal cell differentiation, this effect is not mediated by corticosterone as seen in other reports, and may involve long lasting changes in the local environment, in which pro- inflammatory cytokines are involved.