elevated homocysteine by levodopa is detrimental to neurogenesis in parkinsonian model同型半胱氨酸升高左旋多巴对帕金森模型中神经发生是有害的.pdfVIP

Elevated Homocysteine by Levodopa Is Detrimental to Neurogenesis in Parkinsonian Model 1 2 3 1,4 1 Jin Young Shin , Young-Hwan Ahn , Man-Jeong Paik , Hyun Jung Park , Young H. Sohn , Phil Hyu Lee1,4* 1 Department of Neurology and Brain Research Institute, Yonsei University College of Medicine, Seoul, Korea, 2 Department of Neurosurgery, Ajou University School of Medicine, Suwon, South Korea, 3 Department of Molecular Science and Technology, Ajou University, Suwon, South Korea, 4 Severance Biomedical Science Institute, Yonsei University, Seoul, Korea Abstract Background: Modulation of neurogenesis that acts as an endogenous repair mechanism would have a significant impact on future therapeutic strategies for Parkinson’s disease (PD). Several studies demonstrated dopaminergic modulation of neurogenesis in the subventricular zone (SVZ) of the adult brain. Levodopa, the gold standard therapy for PD, causes an increase in homocysteine levels that induces neuronal death via N-methyl-D-aspartate (NMDA) receptor. The present study investigated whether elevated homocysteine by levodopa treatment in a parkinsonian model would modulate neurogenesis via NMDA receptor signal cascade and compared the effect of levodopa and pramipexol (PPX) on neurogenic activity. Methodology/Principal Findings: Neurogenesis was assessed in vitro using neural progenitor cells (NPCs) isolated from the SVZ and in vivo with the BrdU-injected animal model of PD using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Modulation of homocysteine levels was evaluated using co-cultures of NPCs and astrocytes and PD