The regulated expression of Wnt-1, one member of the wingless/Wnt pathway,
in the brain is critical for many neurodevelopmental processes. Recently, i
t has been reported that the wingless/Wnt pathway participates in a complex
behavioral phenomenon and suggested that this pathway's molecules are cand
idate genes for neuropsychiatric disorders. Thus, we investigated the expre
ssion of Wnt-1 in the hippocampal region, which is believed to be closely i
nvolved in the pathophysiology of schizophrenia, of postmortem brains from
10 schizophrenic and 10 control individuals. Immunohistochemical analysis w
ith polyclonal antibodies recognizing Wnt-1 revealed immunoreactivity prima
rily in the pyramidal cell layer, particularly in CA3 and CA4 regions. We o
bserved a significant elevation in the number of Wnt-1-immunoreactive neuro
ns in the great majority of schizophrenic brains relative to that in contro
ls. The expression of Wnt-1 may be related to cell adhesion, synaptic rearr
angement, and plasticity. Therefore, the increase in Wnt-1 immunoreactivity
in schizophrenic hippocampi suggests an altered plasticity of this structu
re 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.