Impairment of muscarinic transmission in transgenic APPswe/PS1dE9 mice

Machová, E.; Jakubík, J.; Michal, P.; Oksman, M.; Iivonen, H.; Tanila, H.; Doležal, V.

doi:10.1016/j.neurobiolaging.2006.10.029

« Previous Next »Neurobiology of Aging
Volume 29, Issue 3 , Pages 368-378, March 2008

Impairment of muscarinic transmission in transgenic APPswe/PS1dE9 mice

E. Machová
- Department of Neurochemistry, Institute of Physiology CAS, Vídeňská 1083, 14220 Prague 4, Czech Republic
J. Jakubík
- Department of Neurochemistry, Institute of Physiology CAS, Vídeňská 1083, 14220 Prague 4, Czech Republic
P. Michal
- Department of Neurochemistry, Institute of Physiology CAS, Vídeňská 1083, 14220 Prague 4, Czech Republic
M. Oksman
- Department of Neuroscience and Neurology, University of Kuopio, Kuopio, Finland
H. Iivonen
- Department of Neurobiology, A.I. Virtanen Institute, University of Kuopio, Kuopio, Finland
H. Tanila
- Department of Neurobiology, A.I. Virtanen Institute, University of Kuopio, Kuopio, Finland
- Department of Neurology, Kuopio University Hospital, Kuopio, Finland
V. Doležal
- Department of Neurochemistry, Institute of Physiology CAS, Vídeňská 1083, 14220 Prague 4, Czech Republic
- Corresponding author. Tel.: +420 296442287; fax: +420 296442488.

Received 28 June 2006; received in revised form 20 September 2006; accepted 30 October 2006. published online 01 December 2006.

Abstract

We assessed the integrity of cholinergic neurotransmission in parietal cortex of young adult (7 months) and aged (17 months) transgenic APPswe/PS1dE9 female mice compared to littermate controls. Choline acetyltransferase and acetylcholinesterase activity declined age-dependently in both genotypes, whereas both age- and genotype-dependent decline was found in butyrylcholinesterase activity, vesicular acetylcholine transporter density, muscarinic receptors and carbachol stimulated binding of GTPγS in membranes as a functional indicator of muscarinic receptor coupling to G-proteins. Notably, vesicular acetylcholine transporter levels and muscarinic receptor-G-protein coupling were impaired in transgenic mice already at the age of 7 months compared to wild type littermates. Thus, brain amyloid accumulation in this mouse model is accompanied by a serious deterioration of muscarinic transmission already before the mice manifest significant cognitive deficits.

Keywords: Cholinergic neurotransmission, Choline acetyltransferase, Vesicular acetylcholine transporter, Acetylcholinesterase, Butyrylcholinesterase, Muscarinic receptors, G-protein coupling, Transgenic mouse