HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: fj.07-8260comv1 21/14/4028    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Zanardi, A. Articles by Zoli, M. Search for Related Content PubMed PubMed Citation Articles by Zanardi, A. Articles by Zoli, M.

Loss of high-affinity nicotinic receptors increases the vulnerability to excitotoxic lesion and decreases the positive effects of an enriched environment

Alessio Zanardi^*, Rosaria Ferrari^*, Giuseppina Leo^*, Uwe Maskos, Jean-Pierre Changeux and Michele Zoli^*,1

^* Department of Biomedical Sciences, Section of Physiology, and Interuniversity Center for the Study of Aging, University of Modena and Reggio Emilia, Italy; and

CNRS UA 2182–"Récepteurs et Cognition", Institut Pasteur, 28, rue du Dr. Roux, 75724 Paris Cédex 15, France

¹Correspondence: Department of Biomedical Sciences, Section of Physiology, University of Modena and Reggio Emilia, via Campi 287, 41100 Modena, Italy. E-mail: mzoli{at}unimo.it

Pharmacological activation of nicotinic acetylcholine receptors (nAChRs) exerts neuroprotective effects in cultured neurons and the intact animal. Much less is known about a physiological protective role of nAChRs. To understand whether endogenous activation of β2* nAChRs contributes to the maintenance of the functional and morphological integrity of neural tissue, adult β2–/– mice were subjected to in vivo challenges that cause neurodegeneration and cognitive impairment (intrahippocampal injection of the excitotoxin quinolinic acid), or neuroprotection and cognitive potentiation (2-month exposure to an enriched environment). The excitotoxic insult caused an increased deficit in the Morris water maze learning curve and increased loss of hippocampal pyramidal cells in β2–/– mice. Exposure to an enriched environment improved performance in contextual and cued fear conditioning and object recognition tests in β2+/+, whereas the improvement was absent in β2–/– mice. In addition, β2+/+, but not β2–/–, mice exposed to an enriched environment showed a significant hypertrophy of the CA1/3 regions. Thus, lack of β2* nAChRs increased susceptibility to an excitotoxic insult and diminished the positive effects of an enriched environment. These results may be relevant to understanding the pathophysiological consequences of the marked decrease in nAChRs that occurs in neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease.—Zanardi, A., Ferrari, R., Leo, G., Maskos, U., Changeux, J.-P., Zoli, M. Loss of high affinity nicotinic receptors increases the vulnerability to excitotoxic lesion and decreases the positive effects of an enriched environment.

Key Words: nicotinic subunit knockout mice • quinolinic acid • Morris water maze • fear conditioning • hippocampus