Transient elevation of adult hippocampal neurogenesis after dopamine depletion.
Degeneration of the midbrain dopaminergic neurons during Parkinson's disease (PD) may affect remote regions of the brain that are innervated by the projections of these neurons. The dentate gyrus (DG), a site of continuous production of new neurons in the adult hippocampus, receives dopaminergic inputs from the neurons of the substantia nigra (SN). Thus, depletion of the SN neurons during disease or in experimental settings may directly affect adult hippocampal neurogenesis. We show that experimental ablation of dopaminergic neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydopyridine (MPTP) mouse model of PD results in a transient increase in cell division in the subgranular zone (SGZ) of the DG. This increase is evident for the amplifying neural progenitors and for their postmitotic progeny; our results also indicate that MPTP treatment affects division of the normally quiescent stem cells in the SGZ. We also show that l-DOPA, used in the clinical treatment of PD, while attenuating the MPTP-induced death of dopaminergic neurons, does not alter the effect of MPTP on cell division in the DG. Our results suggest that a decrease in dopaminergic signaling in the hippocampus leads to a transient activation of stem and progenitor cells in the DG.
Park
June-Hee
JH
Cold Spring Harbor Laboratory, Cold Spring Harbor, NY 11724, USA.
Enikolopov
Grigori
G
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D053687:Adult Stem Cells / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D016923:Cell Death / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004298:Dopamine / Q000172:deficiency*; D015259:Dopamine Agents / Q000494:pharmacology; D006624:Hippocampus / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D018398:Homeodomain Proteins / Q000378:metabolism; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D039842:Neural Cell Adhesion Molecule L1 / Q000378:metabolism; D055495:Neurogenesis / Q000187:drug effects*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D012794:Sialic Acids / Q000378:metabolism; D013997:Time Factors; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D000098551:Prospero-Related Homeobox 1 Protein
D015259:Dopamine Agents; D018398:Homeodomain Proteins; D039842:Neural Cell Adhesion Molecule L1; D018809:Proliferating Cell Nuclear Antigen; D012794:Sialic Acids; D025521:Tumor Suppressor Proteins; C103469:polysialyl neural cell adhesion molecule; D000098551:Prospero-Related Homeobox 1 Protein; D007980:Levodopa; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D001973:Bromodeoxyuridine; D004298:Dopamine