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EMBO J. 1999 Mar 1;18(5):1235-44.

Increased neurodegeneration during ageing in mice lacking high-affinity nicotine receptors.

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1
CNRS UA D1284, 'Neurobiologie Moléculaire', Institut Pasteur, 28 rue du Dr Roux, 75724 Paris Cédex 15, France.

Abstract

We have examined neuroanatomical, biochemical and endocrine parameters and spatial learning in mice lacking the beta2 subunit of the nicotinic acetylcholine receptor (nAChR) during ageing. Aged beta2(-/-) mutant mice showed region-specific alterations in cortical regions, including neocortical hypotrophy, loss of hippocampal pyramidal neurons, astro- and microgliosis and elevation of serum corticosterone levels. Whereas adult mutant and control animals performed well in the Morris maze, 22- to 24-month-old beta2(-/-) mice were significantly impaired in spatial learning. These data show that beta2 subunit-containing nAChRs can contribute to both neuronal survival and maintenance of cognitive performance during ageing. beta2(-/-) mice may thus serve as one possible animal model for some of the cognitive deficits and degenerative processes which take place during physiological ageing and in Alzheimer's disease, particularly those associated with dysfunction of the cholinergic system.

PMID:
10064590
PMCID:
PMC1171214
DOI:
10.1093/emboj/18.5.1235
[Indexed for MEDLINE]
Free PMC Article
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