Microglia activation in the offspring of prenatal Poly I: C exposed rats: a PET imaging and immunohistochemistry study

Abstract

BackgroundThe well-known ‘pyrotherapy’ of Julius Wagner-Jauregg might be the beginning of the study on the immunological concepts of schizophrenia. As the primary immune effector cells in the brain, microglia play a pivotal role in neuroinflammatory processes. Maternal viral infection during pregnancy is associated with an increased risk for psychiatric disorders with presumed neurodevelopmental origin, including autism spectrum disorders and schizophrenia. The present study was to quantify microglia activation in vivo in the mature offspring of rats exposed to polyriboinosinic–polyribocytidilicacid (Poly I:C) during pregnancy using 11C-PK11195 positron emission tomography (PET) and immunohistochemistry.ObjectiveThe study aimed to quantify microglia activation in vivo in the prefrontal cortex and hippocampus in mature offspring of prenatal Poly I:C exposed rats.MethodsOffspring of Poly I:C-treated dams were the model group, offspring of saline-treated dams were the control group. Behavioural test for two groups was taken by spontaneous activity, prepulse inhibition (PPI) and latent inhibition (LI) test (including active avoidance conditioning task and passive avoidance conditioning task). Randomly selected successful model rats were assessed by behavioural test in the model group and control group rats. 11C-PK11195 micro-PET/CT and immunohistochemistry were performed on the selected rats to measure microglia activation.ResultsThe treatment group showed hyperlocomotion and deficits in PPI and LI compared with the control group. The treatment group also showed an increased 11C-PK11195 uptake ratio in the prefrontal cortex (t=−3.990, p=0.003) and hippocampus (t=−4.462, p=0.001). The number of activated microglia cells was significantly higher in the treatment group than in the control group (hippocampus: t=8.204, p<0.001; prefrontal: t=6.995, p<0.001). Within the treatment group, there were significant correlations between the behavioural parameters and the activation of microglia as measured by PET and immunohistochemistry.ConclusionsThe present study demonstrated microglia activation in vivo in the prefrontal cortex and hippocampus in mature offspring of prenatal Poly I:C exposed rats. This study suggests that microglia activation may play a possible or potential role in the pathogenesis of schizophrenia.