Immunity-linked genes in cognition and schizophrenia

Epidemiological data has clearly identified immune challenges during fetal and early life as a risk factor for developing psychiatric disorders such as schizophrenia and autism. Traditionally the brain was believed to be devoid of immunological responses as its ability to respond by the classical humoral- and cellular- immune responses was absent. During the past years it has been shown that the immune-defense system is active also in the brain, although with clear mechanistic and kinetic differences from other tissues. Similarities between various signaling processes in normal brain activities and the immune system have also been amply documented. Most interestingly, immune deprived animals, e.g. with impaired antigen presentation or altered T cell popul ations, can develop reduced synaptic transmission, cognitive deficits and behavioral abnormalities consistent with those observed in schizophrenia. However, the identity of the key immune genes implicated has remained elusive. Recently, we showed for the first time that synaptic activity in the hippocampus of awake rats most significantly up-regulates immunity-linked genes annotated for MHC class I/II mediated immunity, T-cell mediated immunity and Complement-component mediated immunity. In this proposal, we will functionally characterize the synaptic activity-regulated immune genes in the hippocampus of awake rats, and link the genes to cognitive performances in healthy individuals and to susceptibility and treatment of schizophrenia.