Enriched environment induces cellular plasticity in the adult substantia nigra and improves motor behavior function in the 6-OHDA rat model of Parkinson's disease.
The adult substantia nigra bears the capacity to generate new neural cells throughout adulthood. The mechanisms of cellular plasticity in this brain region remain unknown. In the adult dentate gyrus, dopamine was suggested to be one of the key players in neurogenesis. We therefore investigated nigral cellular plasticity in the 6-OHDA rat model of Parkinson's disease. The absolute numbers of newborn cells in the SN were not affected by dopamine depletion. Interestingly, we found a specific downregulation of generation of newborn nigral astrocytic cells. As enriched environment with physical activity are robust inducers of neuro- and gliogenesis in the adult DG, we investigated the role of these physiological stimuli in nigral cellular plasticity and in motor behavior of 6-OHDA lesioned rats. We describe a significant increase in numbers of newborn NG2-positive and GFAP-positive cells in the SN. Moreover, 6-OHDA lesioned animals living in enriched environment with physical activity for 7 weeks showed improved motor behavior compared to controls under standard conditions. Thus, physiological neurogenic and gliogenic stimuli induce significant microenvironmental changes in the adult SN and improve motor behavior in the 6-OHDA lesion model of PD.
Steiner
Barbara
B
Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch, Robert-Rössle-Str. 10, 13125 Berlin, Germany. barbara.steiner@charite.de
Winter
Christine
C
Hosman
Kai
K
Siebert
Eberhard
E
Kempermann
Gerd
G
Petrus
Dominique S
DS
Kupsch
Andreas
A
D018663:Adrenergic Agents / Q000633:toxicity; D000661:Amphetamine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000941:Antigens / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects; D001973:Bromodeoxyuridine / Q000378:metabolism; D002452:Cell Count; D049109:Cell Proliferation; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D004195:Disease Models, Animal; D004777:Environment; D005260:Female; D005455:Fluorescent Antibody Technique / Q000379:methods; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology*; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D016627:Oxidopamine / Q000633:toxicity; D010300:Parkinson Disease / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D011509:Proteoglycans / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects / Q000473:pathology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D000099216:Chondroitin Sulfate Proteoglycan 4
D018663:Adrenergic Agents; D000661:Amphetamine; D000941:Antigens; D001973:Bromodeoxyuridine; D000697:Central Nervous System Stimulants; D005904:Glial Fibrillary Acidic Protein; D016627:Oxidopamine; D011509:Proteoglycans; D014446:Tyrosine 3-Monooxygenase; D000099216:Chondroitin Sulfate Proteoglycan 4