LACK OF RIC-3 CONGRUENCE WITH BETA2 SUBUNIT-CONTAINING NICOTINIC ACETYLCHOLINE RECEPTORS IN BIPOLAR DISORDER
Neuroscience. 2007 Jul 18; [Epub ahead of print]
Severance EG, Yolken RH
Stanley Division of Developmental Neurovirology, Department of Pediatrics, Johns Hopkins University School of Medicine, 600 North Wolfe Street, Blalock 1105, Baltimore, MD 21287-4933, USA
ABSTRACT
Nicotinic acetylcholine receptor (nAChR) dysfunction occurs in individuals with schizophrenia (SZ) and may also affect individuals with bipolar disorder (BP). The molecular mechanism for these disease-associated cholinergic deficits are not known. In vitro, the protein RIC-3 (resistance to inhibitors of cholinesterase-3) aids the assembly and trafficking of alpha7-nAChRs but has unclear action on the biogenesis of alpha4/beta2-nAChRs. To evaluate RIC-3/nAChR dynamics in diseased and normal human brain tissue, we measured RIC-3, alpha7-, alpha4- and beta2-nACHRs transcript levels in postmortem prefrontal cortex of individuals with SZ (n=31), BP (n=28) and unaffected controls (NC=33). Of the 28 individuals with BP, 20 had a history of psychotic symptoms. We compared relative message abundances between diagnostic groups and tested correlations of RIC-3 with each nAChR message subtype. RIC-3 and alpha 4 messages were significantly increased in BP compared with NC (RIC-3, P