The regulated expression of Wnt-1, one member of the wingless/Wnt pathway, in the brain is critical for many neurodevelopmental processes. Recently, it has been reported that the wingless/Wnt pathway participates in a complex behavioral phenomenon and suggested that this pathway's molecules are candidate genes for neuropsychiatric disorders. Thus, we investigated the expression of Wnt-1 in the hippocampal region, which is believed to be closely involved in the pathophysiology of schizophrenia, of postmortem brains from 10 schizophrenic and 10 control individuals. Immunohistochemical analysis with polyclonal antibodies recognizing Wnt-1 revealed immunoreactivity primarily in the pyramidal cell layer, particularly in CA3 and CA4 regions. We observed a significant elevation in the number of Wnt-1-immunoreactive neurons in the great majority of schizophrenic brains relative to that in controls. The expression of Wnt-1 may be related to cell adhesion, synaptic rearrangement, and plasticity. Therefore, the increase in Wnt-1 immunoreactivity in schizophrenic hippocampi suggests an altered plasticity of this structure in a large proportion of schizophrenic brains. These findings suggest an abnormality of the wingless/Wnt pathway present in the schizophrenic brain and may support the 'neurodevelopmental hypothesis' of schizophrenia. (C) 1999 Elsevier Science B.V. All rights reserved.
