title: Rasagiline ameliorates olfactory deficits in an alpha-synuclein mouse model of Parkinson's disease.
abstract: Impaired olfaction is an early pre-motor symptom of Parkinson's disease. The neuropathology underlying olfactory dysfunction in Parkinson's disease is unknown, however α-synuclein accumulation/aggregation and altered neurogenesis might play a role. We characterized olfactory deficits in a transgenic mouse model of Parkinson's disease expressing human wild-type α-synuclein under the control of the mouse α-synuclein promoter. Preliminary clinical observations suggest that rasagiline, a monoamine oxidase-B inhibitor, improves olfaction in Parkinson's disease. We therefore examined whether rasagiline ameliorates olfactory deficits in this Parkinson's disease model and investigated the role of olfactory bulb neurogenesis. α-Synuclein mice were progressively impaired in their ability to detect odors, to discriminate between odors, and exhibited alterations in short-term olfactory memory. Rasagiline treatment rescued odor detection and odor discrimination abilities. However, rasagiline did not affect short-term olfactory memory. Finally, olfactory changes were not coupled to alterations in olfactory bulb neurogenesis. We conclude that rasagiline reverses select olfactory deficits in a transgenic mouse model of Parkinson's disease. The findings correlate with preliminary clinical observations suggesting that rasagiline ameliorates olfactory deficits in Parkinson's disease.
authors.affiliation: Neuronal Survival Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Science, BMC B11, Lund University, Lund, Sweden. geraldine.petit@med.lu.se
authors.forename: Géraldine H
authors.initials: GH
authors.lastname: Petit
authors.forename: Elijahu
authors.initials: E
authors.lastname: Berkovich
authors.forename: Mark
authors.initials: M
authors.lastname: Hickery
authors.forename: Pekka
authors.initials: P
authors.lastname: Kallunki
authors.forename: Karina
authors.initials: K
authors.lastname: Fog
authors.forename: Cheryl
authors.initials: C
authors.lastname: Fitzer-Attas
authors.forename: Patrik
authors.initials: P
authors.lastname: Brundin
mesh_terms: D000367:Age Factors; D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D007189:Indans / Q000494:pharmacology* / Q000627:therapeutic use; D008570:Memory, Short-Term; D051379:Mice; D008822:Mice, Transgenic; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000857:Olfaction Disorders / Q000188:drug therapy*; D009830:Olfactory Bulb / Q000187:drug effects / Q000473:pathology; D010300:Parkinson Disease / Q000188:drug therapy*; D012903:Smell / Q000187:drug effects; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D007189:Indans; D008996:Monoamine Oxidase Inhibitors; D051844:alpha-Synuclein; C031967:rasagiline