Disturbed social behavior and motivation in rats selectively bred for deficient sensorimotor gating
Deficient prepulse inhibition (PPI) of startle reflects disturbed sensorimotor gating found in certain neuropsychiatric disorders. We here tested whether rats selectively bred for deficient PPI are deteriorated in behavioral paradigms used to model negative symptoms of schizophrenia. Rats with low PPI preferred standard rat-chow when having the choice between lever-pressing for reward-pellets or freely available rat-chow, suggesting reduced motivation. Additionally, these rats show deteriorated social behavior during interaction with a juvenile rat. Rats selectively bred for low PPI may therefore be used as a model to study the biological mechanisms and therapeutic strategies of negative sy…
The genetic contribution of the NO system at the glutamatergic post-synapse to schizophrenia: Further evidence and meta-analysis
NO is a pleiotropic signaling molecule and has an important role in cognition and emotion. In the brain, NO is produced by neuronal nitric oxide synthase (NOS-I, encoded by NOS1) coupled to the NMDA receptor via PDZ interactions; this protein-protein interaction is disrupted upon binding of NOS1 adapter protein (encoded by NOS1AP) to NOS-I. As both NOS1 and NOS1AP were associated with schizophrenia, we here investigated these genes in greater detail by genotyping new samples and conducting a meta-analysis of our own and published data. In doing so, we confirmed association of both genes with schizophrenia and found evidence for their interaction in increasing risk towards disease. Our stron…
Hippocampal overexpression of Nos1ap promotes endophenotypes related to mental disorders
Abstract Background Nitric oxide synthase 1 adaptor protein (NOS1AP; previously named CAPON) is linked to the glutamatergic postsynaptic density through interaction with neuronal nitric oxide synthase (nNOS). NOS1AP and its interaction with nNOS have been associated with several mental disorders. Despite the high levels of NOS1AP expression in the hippocampus and the relevance of this brain region in glutamatergic signalling as well as mental disorders, a potential role of hippocampal NOS1AP in the pathophysiology of these disorders has not been investigated yet. Methods To uncover the function of NOS1AP in hippocampus, we made use of recombinant adeno-associated viruses to overexpress muri…