Neonatal exposure to MK801 induces structural reorganization of the central nervous system

Schizophrenia, a progressive disorder displaying widespread pathological changes, is associated with the loss of glutamatergic function and selective loss of cytoskeletal proteins, such as MAP2, in regions severely affected by this disease. As schizophrenia is associated with perinatal brain trauma, we monitored changes in several functionally different proteins following injury-promoting MK801 blockade of N-methyl-D-aspartate receptors in neonatal rats. Within the somatosensory cortex, MK801 triggered robust, caspase-3-dependent apoptotic injury, reduced expression of cytoskeletal proteins MAP2 and tau, and increased synapse associated protein SNAP25. Thus, both neuronal injury and loss of structural elements important for successful cell-cell contact may reorganize brain circuitry, which at later ages could promote similar behavioral changes observed in schizophrenia.