Locus coeruleus degeneration exacerbates olfactory deficits in APP/PS1 transgenic mice.
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.
Laboratoire Neurosciences Sensorielles, Comportement, Cognition, UMR5020 CNRS, University Lyon1, University of Lyon, Lyon, France.
Nolwen L
NL
Rey
Daniel
D
Jardanhazi-Kurutz
Dick
D
Terwel
Markus P
MP
Kummer
Francois
F
Jourdan
Anne
A
Didier
Michael T
MT
Heneka
D000544:Alzheimer Disease / Q000150:complications / Q000473:pathology* / Q000503:physiopathology*; D000818:Animals; D001284:Atrophy / Q000000981:diagnostic imaging / Q000473:pathology; D005260:Female; D008125:Locus Coeruleus / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D019636:Neurodegenerative Diseases / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D000857:Olfaction Disorders / Q000150:complications / Q000473:pathology* / Q000503:physiopathology*; D011877:Radionuclide Imaging; D012903:Smell