title: Physical exercise counteracts MPTP-induced changes in neural precursor cell proliferation in the hippocampus and restores spatial learning but not memory performance in the water maze.
abstract: Parkinson's disease (PD) is characterized by a continuous loss of dopaminergic neurons in the substantia nigra, which not only leads to characteristic motor symptoms but also to cognitive impairments. Physical exercise has been shown to improve hippocampus-dependent cognitive functions in PD patients. Animal studies have demonstrated the involvement of adult hippocampal neurogenesis in exercise-induced improvements of visuo-spatial learning and memory. Here, we investigated the direct impact of voluntary wheel running on hippocampal neurogenesis and spatial learning and memory in the Morris water maze (MWM) using the1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. We also analyzed striatal and hippocampal dopamine transmission and mRNA expression levels of dopamine receptors. We show that MPTP-induced spatial learning deficits were alleviated by short-term physical exercise but not MPTP-induced spatial memory impairments in either exercise intervention group. Neural precursor proliferation was transiently altered in MPTP-treated mice, while the cell survival was increased by exercise. Dopamine was progressively depleted by MPTP and its turnover altered by exercise. In addition, gene expression of dopamine receptor D1/D5 was transiently upregulated following MPTP treatment but not affected by physical exercise. Our findings suggest that physical exercise benefits spatial learning but not memory performance in the MWM after MPTP-induced dopamine depletion by restoring precursor cell proliferation in the hippocampus and influencing dopamine transmission. This adds to the understanding of cognitive decline and mechanisms for potential improvements by physical exercise in PD patients.
authors.affiliation: Charité University Medicine Berlin, Department of Neurology, Berlin, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Klein
authors.affiliation: Charité University Medicine Berlin, Department of Neurology, Berlin, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Rasińska
authors.affiliation: Charité University Medicine Berlin, Department of Neurology, Berlin, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Empl
authors.affiliation: Charité University Medicine Berlin, Department of Neurology, Berlin, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Sparenberg
authors.affiliation: Charité University Medicine Berlin, Department of Neurology, Berlin, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Poshtiban
authors.affiliation: Charité University Medicine Berlin, Department of Neurology, Berlin, Germany.
authors.forename: E G
authors.initials: EG
authors.lastname: Hain
authors.affiliation: Charité University Medicine Berlin, Department of Neurology, Berlin, Germany.
authors.forename: D
authors.initials: D
authors.lastname: Iggena
authors.affiliation: Humboldt University, Department of Neurobiology, Berlin, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Rivalan
authors.affiliation: Humboldt University, Department of Neurobiology, Berlin, Germany.
authors.forename: Y
authors.initials: Y
authors.lastname: Winter
authors.affiliation: Charité University Medicine Berlin, Department of Neurology, Berlin, Germany. Electronic address: barbara.steiner@charite.de.
authors.forename: B
authors.initials: B
authors.lastname: Steiner
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D000089622:Doublecortin Domain Proteins; D005260:Female; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology*; D020267:MPTP Poisoning / Q000139:chemically induced / Q000534:rehabilitation*; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D064231:Nestin / Q000235:genetics / Q000378:metabolism; D058953:Neural Stem Cells / Q000187:drug effects / Q000502:physiology*; D009479:Neuropeptides / Q000378:metabolism; D010805:Physical Conditioning, Animal; D011930:Reaction Time / Q000187:drug effects; D065853:Spatial Learning / Q000502:physiology*
chemical_list: D000089622:Doublecortin Domain Proteins; D008869:Microtubule-Associated Proteins; C577485:Nes protein, mouse; D064231:Nestin; D009479:Neuropeptides; D015102:3,4-Dihydroxyphenylacetic Acid; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D001973:Bromodeoxyuridine; D004298:Dopamine
keywords: Dopamine; Hippocampus; MPTP; Neurogenesis; Parkinson’s disease; Physical exercise