title: Long-term treatment with L-DOPA or pramipexole affects adult neurogenesis and corresponding non-motor behavior in a mouse model of Parkinson's disease.
abstract: Non-motor symptoms such as hyposmia and depression are often observed in Parkinson's disease (PD) and can precede the onset of motor symptoms for years. The underlying pathological alterations in the brain are not fully understood so far. Dysregulation of adult neurogenesis in the dentate gyrus of the hippocampus and the olfactory bulb has been recently suggested to be implicated in non-motor symptoms of PD. However, there is so far no direct evidence to support the relationship of non-motor symptoms and the modulation of adult neurogenesis following dopamine depletion and/or dopamine replacement. In this study, we investigated the long-term effects of l-DOPA and pramipexole, a dopamine agonist, in a mouse model of bilateral intranigral 6-OHDA lesion, in order to assess the impact of adult neurogenesis on non-motor behavior. We found that l-DOPA and pramipexole can normalize decreased neurogenesis in the hippocampal dentate gyrus and the periglomerular layer of the olfactory bulb caused by a 6-OHDA lesion. Interestingly, pramipexole showed an antidepressant and anxiolytic effect in the forced swim test and social interaction test. However, there was no significant change in learning and memory function after dopamine depletion and dopamine replacement, respectively.
authors.affiliation: Department of Neurology, Philipps-University, Marburg, Germany.
authors.forename: W-H
authors.initials: WH
authors.lastname: Chiu
authors.affiliation: Department of Neurology, Philipps-University, Marburg, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Depboylu
authors.affiliation: Department of Neurology, Philipps-University, Marburg, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Hermanns
authors.affiliation: Department of Neurology, Philipps-University, Marburg, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Maurer
authors.affiliation: Department of Neurology, Philipps-University, Marburg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Windolph
authors.affiliation: Department of Neurology, Philipps-University, Marburg, Germany.
authors.forename: W H
authors.initials: WH
authors.lastname: Oertel
authors.affiliation: Department of Neurology, Philipps-University, Marburg, Germany. Electronic address: ries@med.uni-marburg.de.
authors.forename: V
authors.initials: V
authors.lastname: Ries
authors.affiliation: Department of Neurology, Philipps-University, Marburg, Germany; Department of Neurology, Technical University, Munich, Germany; German Center for Neurodegenerative Diseases, Munich, Germany.
authors.forename: G U
authors.initials: GU
authors.lastname: Höglinger
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D001007:Anxiety / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D052160:Benzothiazoles / Q000494:pharmacology*; D003863:Depression / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D007980:Levodopa / Q000494:pharmacology*; D008297:Male; D008810:Mice, Inbred C57BL; D055495:Neurogenesis / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D009830:Olfactory Bulb / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology / Q000523:psychology; D000077487:Pramipexole; D011897:Random Allocation
chemical_list: D000978:Antiparkinson Agents; D052160:Benzothiazoles; D007980:Levodopa; D000077487:Pramipexole; D016627:Oxidopamine
keywords: 6-Hydroxydopamine; Adult neurogenesis; Hippocampal dentate gyrus; Olfactory bulb; Parkinson's disease; Pramipexole; l-DOPA