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

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Abstract
We have examined neuroanatomical, biochemical and endocrine parameters and spatial learning in mice lacking the β2 subunit of the nicotinic acetylcholine receptor (nAChR) during ageing. Aged β2−/− 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 β2−/− mice were significantly impaired in spatial learning. These data show that β2 subunit‐containing nAChRs can contribute to both neuronal survival and maintenance of cognitive performance during ageing. β2−/− 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.