Abnormalities of presynaptic protein CDCrel-1 in striatum of rats reared in social isolation: relevance to neural connectivity in schizophrenia.
Post-weaning social isolation-rearing of rats leads to behavioural and neurochemical sequelae that model aspects of schizophrenia, and it may be useful to test hypotheses related to putative molecular mechanisms of the illness. In humans, the presynaptic protein CDCrel-1 represents an interesting candidate molecule for the mechanism and aetiology of schizophrenia. CDCrel-1 modulates dopamine neurotransmission, binds to the SNARE protein syntaxin and maps onto a region of chromosome 22q11 deleted in velo-cardio-facial and DiGeorge syndromes, which are associated with increased prevalence of schizophrenia. Using the isolation-rearing model, we measured immunoreactivity of the synaptic proteins CDCrel-1, synaptophysin and syntaxin. Male, Sprague-Dawley rats were raised in groups or in isolation for 12 weeks from weaning. Synaptic protein immunoreactivities were measured in striatal and hippocampal homogenates, using a sensitive enzyme-linked immunoadsorbent assay with monoclonal antibodies. Isolation-rearing produced region- and protein-specific effects. CDCrel-1 immunoreactivity was significantly lower in the striatum and marginally higher in the hippocampus of isolation-reared compared with socially reared animals. There were no statistically significant differences in synaptophysin immunoreactivity in either region. Confocal microscopy demonstrated a high degree of colocalization between the two presynaptic proteins. In striatum, a robust relationship between CDCrel-1 and syntaxin immunoreactivities was observed in socially reared rats, this was lost in the isolation-reared animals. Altered levels of the septin CDCrel-1 in isolation-reared rats may contribute to changes in neuronal connectivity and neurotransmission, and suggest a potential role for CDCrel-1 in schizophrenia related to chromosome 22q11 deletion syndrome.
Barr
Alasdair M
AM
Centre for Complex Disorders, University of British Columbia, 828 West 10th Avenue, Vancouver, BC, Canada V5Z 1L8.
Young
Clint E
CE
Sawada
Ken
K
Trimble
William S
WS
Phillips
Anthony G
AG
Honer
William G
WG
D000818:Animals; D001522:Behavior, Animal; D015153:Blotting, Western / Q000379:methods; D018797:Cell Cycle Proteins / Q000276:immunology / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D006624:Hippocampus / Q000378:metabolism; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D017072:Neostriatum / Q000378:metabolism*; D050765:Qa-SNARE Proteins; D051381:Rats; D017207:Rats, Sprague-Dawley; D058112:Septins; D012934:Social Isolation; D016708:Synaptophysin / Q000378:metabolism
D018797:Cell Cycle Proteins; D008565:Membrane Proteins; D050765:Qa-SNARE Proteins; D016708:Synaptophysin; C491613:Septin5 protein, rat; D058112:Septins