Disrupted-in-Schizophrenia 1 (DISC1) Overexpression and Juvenile Immune Activation Cause Sex-Specific Schizophrenia-Related Psychopathology in Rats

ConclusionsOur findings indicate that overexpressed human DISC1 with schizophrenia-related polymorphisms × JIA by the LPS model is a useful tool that can be used in future studies to investigate the two-hit, synaptic pruning hypothesis of schizophrenia. The sex-specific behavioral phenotype that we observed here is in line with the sex-biased symptomology of schizophrenia. Future studies should focus more on the factors that influence brain maturation during extremely vulnerable juvenile and early adolescent periods. Such challenges, as indicated here, can interact with the genetic susceptibility factors to synergistically induce schizophrenia-related disruptions in adulthood.Ethics StatementAll experiments were conducted in conformity with the Animal Protection Law of the Federal Republic of Germany as well as the European Communities Council 2010 Directive (2010/63/EU) and were approved by local authorities (Regierung von Mittelfranken).Author ContributionsCM, TU, and JH designed the study. CK generated the transgenic rat line. TU, JS, AW, IZ, and MD conducted behavioral experiments. GK performed the neurochemical measurements. TU, AW, and CM did the statistical analysis and wrote the first draft of the manuscript. SvH, JK, JH, and CK revised the manuscript. All authors contributed to and approved the final form of the manuscript.FundingThis work was supported by the German Research Foundation (DFG) grant MU 2789/7-1.Conflict of Interest StatementThe authors declare th...
Source: Frontiers in Psychiatry - Category: Psychiatry Source Type: research