NOVEL ALPHA7 NICOTINIC RECEPTOR ISOFORMS AND DEFICIENT CHOLINERGIC TRANSCRIPTION IN SCHIZOPHRENIA
Genes Brain Behav. 2007 May 14; [Epub ahead of print]
Severance EG, Yolken RH
Stanley Division of Developmental Neurovirology, Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA
ABSTRACT
Abnormal alpha7 nicotinic acetylcholine receptor activity contributes to sensory gating and cognitive deficits in schizophrenic individuals. Negligible differences in alpha7 mRNA levels between disease and control states have led to conclusions that cholinergic dysfunction in schizophrenia (SZ) must occur post-transcriptionally. Alternatively, we propose that the dysregulation of splice variants of the alpha7 receptor could account for cholinergic deficiencies observed in this disease. Here, we isolated multiple alpha7 splice variants including exon deletions and those associated with a novel 124-127 base insertion following exon 4. Transcripts containing this new exon originated from sense strand-oriented RNA (vs. antisense), and in silico translations produces putative subunits with unique amino termini. Quantitative real-time polymerase chain reaction analyses indicated that one novel isoform was significantly downregulated (P