Expression of complexin I and II mRNAs and their regulation by antipsychotic drugs in the rat forebrain.
Complexin (cx) I and II are homologous synaptic protein genes which are differentially expressed in mouse and human brain and differentially affected in schizophrenia. We characterized the distribution of cx I and II mRNAs in rat forebrain and examined whether their abundance, or the transcript of the synaptic marker synaptophysin, is affected by 14 days' administration of antipsychotic drugs (haloperidol, chlorpromazine, risperidone, olanzapine, or clozapine). Cx I mRNA predominated in medial habenula, medial septum-diagonal band complex, and thalamus, whereas cx II mRNA was more abundant in most other regions, including isocortex and hippocampus. Within the hippocampus, cx I mRNA was primarily expressed by interneurons and cx II mRNA by granule cells and pyramidal neurons. Localized cx II mRNA signal was seen in the dentate gyrus molecular layer, suggestive of its transport into granule cell dendrites. Antipsychotic treatment produced selective, modest effects on cx mRNA expression. Cx I mRNA was elevated by olanzapine in dorsolateral striatum and frontoparietal cortex, while the abundance of cx II mRNA relative to cx I mRNA was decreased in both areas by olanzapine and haloperidol. Chlorpromazine increased cx II mRNA in frontoparietal cortex and synaptophysin mRNA in dorsolateral striatum. In summary, the data have implications both for understanding the effects of antipsychotic medication on synaptic organization, and for synaptic protein expression studies in patients treated with the drugs.
Eastwood
S L
SL
University Department of Psychiatry, Warneford Hospital, Oxford, UK. sharon.eastwood@psych.ox.ac.uk
Burnet
P W
PW
Harrison
P J
PJ
D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D016548:Prosencephalon / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016708:Synaptophysin / Q000235:genetics; D014018:Tissue Distribution
D033942:Adaptor Proteins, Vesicular Transport; D014150:Antipsychotic Agents; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D016708:Synaptophysin; C095992:complexin I; C095993:complexin II