Minocycline alleviates behavioral deficits and inhibits microglial activation in the offspring of pregnant mice after administration of polyriboinosinic-polyribocytidilic acid.

Epidemiological studies have indicated that maternal infection during pregnancy may lead to a higher incidence of schizophrenia in the offspring. Activation of microglia is a key event in the reaction of the cerebral immune system to pathological changes. It can be hypothesized that microglia contribute to the neuropathology of schizophrenia. In this study, at embryonic day (ED) 9 pregnant mice were treated with intraperitoneal injection of polyriboinosinic-polyribocytidilic acid (Poly I:C) at a single dose of 20 mg/kg. At postnatal day 42, descendants were treated with minocycline (40 mg/kg) or saline for consecutive 14 days. Behavioral changes (locomotor activity, social interaction, and prepulse inhibition) were examined and the number of microglia was assessed after the treatment. The adult offspring exposed to Poly I:C at ED 9 showed behavioral changes (hyperlocomotion, deficits in social interaction and prepulse inhibition) and significant microglial activation in these brain areas (hippocampus, thalamus, and cerebral cortex) compared to those in saline-injected group. Moreover, minocycline attenuated the behavioral deficits and inhibited the activated microglia. These findings suggest that maternal infection may contribute to microglial activation in the offspring. In addition, the effect of minocycline in this immune model may be related to the inhibition of microglial activation.