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 α7 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 α4, α3, α7, α5 and β2 nicotinic receptors were investigated in the brains of α7 deficient (α7 −/−), α7 heterozygous null (α7 +/−) and α7 wild-type (α7 +/+) mice from postnatal days (P) 7–84. The specific binding of [3H] cytisine and [3H] epibatidine, as well as the expressions of α4 and α3 nicotinic receptor subunits at mRNA and protein levels, were significantly increased in the cortex and hippocampus of α7 −/− and α7 +/− mice compared with α7 +/+ mice. Furthermore, the α4 and α3 nicotinic acetylcholine receptor (nAChR) subunits appeared to co-assemble with the α5 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 α4, α3-containing nAChRs, co-assembled with the α5 nAChR subunit, may contribute to the normal brain development of α7 −/− and α7 +/− mice.