Effect of memantine on the α7 neuronal nicotinic receptors, synaptophysin- and low molecular weight MAP-2 levels in the brain of transgenic mice over-expressing human acetylcholinesterase

Transgenic mice over-expressing human acetylcholinesterase ( hAChETg) display memory impairments, cholinergic deficits and reduced dendritic branching. In this study, we found a reduced number of N-Methyl-D-Aspartate ( NMDA) binding sites and reduced levels of low molecular weight (LMW) microtubule associated protein 2 (MAP-2), in addition to an increased number of alpha4 and alpha7 nicotinic receptor ( nAChR) binding sites in the brain of hAChETg mice. Treatment with memantine, 20 mg/kg/day during 14 days, significantly increased the number of [I-125] alphabungarotoxin (alpha7 nAChR) binding sites in the frontal- and retrosplenial cortex of hAChE-Tg mice and synaptophysin- and LMW MAP-2 levels in the cortex of both hAChE-Tg and FVB/N controls. The findings reveal an alteration of the glutamatergic system in hAChE-Tg mice. Whether the effect of memantine on alpha7 nAChRs, synaptophysin- and LMW MAP-2 levels is a direct effect, or an indirect effect via the NMDA receptors, has to be further evaluated.