Article
- The EMBO Journal (1999) 18, 1235 - 1244
- doi:10.1093/emboj/18.5.1235
Increased neurodegeneration during ageing in mice lacking high-affinity nicotine receptors
Michele Zoli1,2,5, Marina R. Picciotto1,3,5, Rosaria Ferrari2, Daniela Cocchi4 and Jean-Pierre Changeux1
- CNRS UA D1284, 'Neurobiologie Moléculaire', Institut Pasteur, 28 rue du Dr Roux, 75724 Paris Cédex 15, France
- Department of Biomedical Sciences, Section of Physiology, and Interuniversity Center for the Study of Aging, University of Modena, Italy
- Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA
- Department of Biomedical Sciences and Biotechnology, University of Brescia, Italy
- M.Zoli and M.R.Picciotto contributed equally to this work
Correspondence to:
Jean-Pierre Changeux, E-mail: changeux@pasteur.fr
Received 24 November 1998; Accepted 5 January 1999; Revised 5 January 1999
Abstract
We have examined neuroanatomical, biochemical and endocrine parameters and spatial learning in mice lacking the 
2 subunit of the nicotinic acetylcholine receptor (nAChR) during ageing. Aged 2-/- 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 2-/- mice were significantly impaired in spatial learning. These data show that 2 subunit-containing nAChRs can contribute to both neuronal survival and maintenance of cognitive performance during ageing. 2-/- 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.
Keywords:
- ageing,
- gliosis,
- homologous recombination,
- neurodegeneration,
- nicotinic acetylcholine receptor
