[en] Neuronal loss in the locus coeruleus (LC) is 1 of the early pathological events in Alzheimer's disease (AD). Projections of noradrenergic neurons of the LC innervate the olfactory bulb (OB). Because olfactory deficits have been reported in early AD, we investigated the effect of induced LC degeneration on olfactory memory and discrimination in an AD mouse model. LC degeneration was induced by treating APP/PS1 mice with N-(2-chloroethyl)-N-ethyl-bromo-benzylamine (DSP4) repeatedly between 3 and 12 months of age. Short term odor retention, ability for spontaneous habituation to an odor, and spontaneous odor discrimination were assessed by behavioral tests. DSP4 treatment in APP/PS1 mice resulted in an exacerbation of short term olfactory memory deficits and more discrete weakening of olfactory discrimination abilities, suggesting that LC degeneration contributes to olfactory deficits observed in AD. Importantly, DSP4 treatment also increased amyloid β (Aβ) deposition in the olfactory bulb of APP/PS1 mice, which correlated with olfactory memory, not with discrimination deficits.
Disciplines :
Neurology
Author, co-author :
Rey, Nolwen L; Laboratoire Neurosciences Sensorielles, Comportement, Cognition, UMR5020 CNRS, University Lyon1, University of Lyon, Lyon, France
Jardanhazi-Kurutz, Daniel; University of Bonn, Department of Neurology, Clinical Neurosciences Unit, Bonn, Germany
Terwel, Dick; University of Bonn, Department of Neurology, Clinical Neurosciences Unit, Bonn, Germany
Kummer, Markus P; University of Bonn, Department of Neurology, Clinical Neurosciences Unit, Bonn, Germany
Jourdan, Francois; Laboratoire neurosciences sensorielles, Comportement, cognition, UMR5020 CNRS, University Lyon 1, University of Lyon, Lyon, France
Didier, Anne; Laboratoire neurosciences sensorielles, Comportement, cognition, UMR5020 CNRS, University Lyon 1, University of Lyon, Lyon, France
HENEKA, Michael ; University of Bonn, Department of Neurology, Clinical Neurosciences Unit, Bonn, Germany
External co-authors :
yes
Language :
English
Title :
Locus coeruleus degeneration exacerbates olfactory deficits in APP/PS1 transgenic mice.
Competence Network Degenerative Dementias of the German Federal Ministry of Education
Funding text :
This study was supported by “Cluster Handicap, Vieillissement, Neurosciences”, Région Rhône-Alpes, France (to NR and AD) and by the Competence Network Degenerative Dementias of the German Federal Ministry of Education (grant number 01 GI 0720 ) to MTH.
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