Regulation of synapses II by dopaminergic mechanisms

Synapsin II is a member of the neuronal phosphoprotein family. These phosphoproteins are evolutionarily conserved in vertebrate and invertebrate organisms and are important in a variety of cellular functions, including neurotransmitter release at the presynaptic terminal, synaptogenesis, and the maintenance of synaptic vesicular pools. The synapsin II gene is located on chromosome 3p25 and has been implicated as a candidate gene for schizophrenia. Recent reports from our laboratory have demonstrated that synapsin II expression is regulated by dopamine D1 and D2 receptors. Specifically, stimulation of the dopamine D1 receptor leads to increased synapsin II gene expression involving the AP-2α transcription factor located at the promoter region. Additionally, robust increases in synapsin II in the striatum caused by the dopamine D2 receptor antagonist haloperidol may be related to the induction of extrapyramidal side effects, whereas greater increases of synapsin II in the medial prefrontal cortex by atypical antipsychotic drugs such as olanzapine may be related to thisdrugs' therapeutic effects. At the preclinical level, selective knockdown of synapsin II by antisense or siRNA technology in the medial prefrontal cortex leads to the development of schizophrenia-like behavioural abnormalities in the rat, suggesting a causal role for this phosphoprotein in the pathophysiology of schizophrenia. Collectively, these studies suggest that synapsin II may potentially serve as a novel therapeutic target for this mental illness. © 2012 Nova Science Publishers, Inc.