Received for publication November 14, 2005.
Revised December 9, 2005.
Accepted for publication December 12, 2005.

Effect of Subchronic Treatment of Memantine, Galantamine and Nicotine in the Brain of APPswe Transgenic Mice

Abstract

Increasing number of studies suggests that the present clinical therapy used in Alzheimer's disease (AD), in addition to having a symptomatic effect, also may interact with the ongoing neuropathological processes in the brain. The aim of this study was to investigate the effect of the cholinesterase inhibitor galantamine and the N-Methyl-D-Aspartate (NMDA) antagonist memamtine, in comparison to nicotine, on the neuropathology of Tg2576 transgenic mice (APPswe). Non-transgenic and APPswe mice at 10 months of age were treated subcutaneously with saline, memantine, galantamine or nicotine for 10 days. Nicotine reduced the guanidinium-soluble A levels by 46-66%, while the intracellular A levels remained unchanged. Treatment with nicotine also resulted in less GFAP immunoreactive astrocytes around the plaques, increased levels of synaptophysin and increased number of 7 nicotinic acetylcholine receptors (nAChRs) in the cortex of APPswe transgenic mice. Galantamine treatment caused an increase in the cortical levels of synaptophysin in the APPswe mice. Memantine treatment reduced the total cortical levels of membrane-bound APP (45-55 %) in both transgenic and non-transgenic mice, which eventually may decrease the level of A. In conclusion, galantamine, memantine and nicotine have different interactions with A processes, 7 nAChRs and NMDA receptors in APPswe mice. These different effects might have therapeutic relevance and this knowledge might be applicable to the development of new effective therapeutic strategies for AD.

Key words: APPswe transgenic mice, Beta-amyloid, NMDA receptors, Synaptophysin, Treatment, nAChRs