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Working memory deficits and related disinhibition of the cAMP/PKA/CREB are alleviated by prefrontal α4β2*-nAChRs stimulation in aged mice.
MedLine Citation:
PMID:  23352115     Owner:  NLM     Status:  Publisher    
The present study investigates in aged mice the working memory (WM) enhancing potential of the selective α4β2* nicotinic receptor agonist S 38232 as compared with the cholinesterase inhibitor donepezil, and their effect on cAMP response element binding protein (CREB) phosphorylation (pCREB) as a marker of neuronal activity. We first showed that aged mice exhibit a WM deficit and an increase of pCREB in the prelimbic cortex (PL) as compared with young mice, whereas no modification appears in the CA1. Further, we showed that systemic administration of S 38232 restored WM in aged mice and alleviated PL CREB overphosphorylation. Donepezil alleviated age-related memory deficits, however, by increasing pCREB in the CA1, while pCREB in PL remained unaffected. Finally, whereas neuronal inhibition by lidocaine infusion in the PL appeared deleterious in young mice, the infusion of Rp-cAMPS (a compound known to inhibit CREB phosphorylation) or S 38232 rescued WM in aged animals. Thus, by targeting the α4β2*-nicotinic receptor of the PL, S 38232 alleviates PL CREB overphosphorylation and restores WM in aged mice, which opens new pharmacologic perspectives of therapeutic strategy.
Matthias Vandesquille; Mathieu Baudonnat; Laurence Decorte; Caroline Louis; Pierre Lestage; Daniel Béracochéa
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-23
Journal Detail:
Title:  Neurobiology of aging     Volume:  -     ISSN:  1558-1497     ISO Abbreviation:  Neurobiol. Aging     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-28     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8100437     Medline TA:  Neurobiol Aging     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 Elsevier Inc. All rights reserved.
CNRS, Univ. Bordeaux, INCIA UMR 5287, Bordeaux, France; Institut de Recherches SERVIER (IDRS), Croissy-sur-Seine, France.
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