Postnatal upregulation of α4 and α3 nicotinic receptor subunits in the brain of α7 nicotinic receptor-deficient mice

The nicotinic receptor subtypes are important for several physiological functions in brain and may therefore play a critical role in brain development. The alpha 7 nicotinic receptors which have high Ca2+ permeability are important for cognitive, neuroprotective and trophic functions. In this study, the brain development and the expression of alpha 4, alpha 3, alpha 7, alpha 5 and beta 2 nicotinic receptors were investigated in the brains of alpha 7 deficient (alpha 7 -/-), alpha 7 heterozygous null (alpha 7 +/-) and alpha 7 wild-type (alpha 7 +/+) mice from postnatal days (P) 7-84. The specific binding of [H-3] cytisine and [H-3] epibatidine, as well as the expressions of alpha 4 and alpha 3 nicotinic receptor subunits at mRNA and protein levels, were significantly increased in the cortex and hippocampus of alpha 7 -/- and alpha 7 +/- mice compared with alpha 7 +/+ mice. Furthermore, the alpha 4 and alpha 3 nicotinic acetylcholine receptor (nAChR) subunits appeared to co-assemble with the alpha 5 nAChR subunit in these above brain regions of these mice. No significant change in synaptophysin level was observed. These data suggest that increased levels of alpha 4, alpha 3-containing nAChRs, co-assembled with the alpha 5 nAChR subunit, may contribute to the normal brain development of alpha 7 -/- and alpha 7 +/- mice. (C) 2007 IBRO. Published by Elsevier Ltd. All rights reserved.