Full-length ArticleSchizophrenia associated sensory gating deficits develop after adolescent microglia activation

- Prenatal immune activation (PIA) led to reduction of PPI in female adult offspring.
- Schizophrenic-like behavior (PPI deficits) developed not before adulthood.
- PIA leads to a pro-inflammatory microglia phenotype in adolescent females.
- Microglia activation did not persist until adulthood.
- Microglia activation was absent in behaviorally unaffected male descendants.Please note: Conclusions on the peripheral immune status during adolescence are limited to the responsiveness of PBMCs to mitogen-stimulation and do not reflect the in-vivo situation directly.

Maternal infection during pregnancy is a well-established risk factor for schizophrenia in the adult offspring. Consistently, prenatal Poly(I:C) treatment in mice has been validated to model behavioral and neurodevelopmental abnormalities associated with schizophrenia. By using the Poly(I:C) BALB/c mouse model, we investigated the functional profile of microglia by flow cytometry in relation to progressive behavioral changes from adolescence to adulthood.Prenatal Poly(I:C) treatment induced the expected sensory gating deficits (pre-pulse inhibition (PPI) of the acoustic startle response) in 100 day-old adult offspring, but only in female not in male descendants. No PPI-deficits were present in 30 day-old adolescent mice. Sensory gating deficits in adult females were preceded by a strong M1-type microglia polarization pattern during puberty as determined by flow cytometric analysis of multiple pro- and anti-inflammatory surface markers. Microglia activation in females did not persist until adulthood and was absent in behaviorally unaffected male descendants. Further, the specific activation pattern of microglia was not mirrored by a similar activation of peripheral immune cells. We conclude that prenatal Poly(I:C) treatment induces post pubertal deficits in sensory gating which are specifically preceded by a pro-inflammatory activation pattern of microglia during puberty.