The rs6265 single nucleotide polymorphism (SNP) in the gene for brain-derived neurotrophic factor is a common variant that alters therapeutic outcomes for individuals with Parkinson’s disease (PD). We previously investigated the effects of this SNP on the experimental therapeutic approach of neural grafting, demonstrating that young adult parkinsonian rats carrying the variant Met allele exhibited enhanced graft function compared to wild-type rats and also exclusively developed aberrant graft-induced dyskinesias (GID). Aging is the primary risk factor for PD and reduces graft efficacy. Here we investigated whether aging interacts with this SNP to further alter cell transplantation outcomes. We hypothesized that aging would reduce enhancement of graft function associated with this genetic variant and exacerbate GID in all grafted subjects. Unexpectedly, beneficial graft function was maintained in aged rs6265 subjects. However, aging was permissive to GID induction, regardless of genotype, with the greatest incidence and severity found in rs6265-expressing animals.

脑源性神经营养因子基因中的 rs6265 单核苷酸多态性 (SNP) 是一种常见变异，可改变帕金森病 (PD) 患者的治疗结果。我们之前研究了该 SNP 对神经移植实验治疗方法的影响，证明携带变体 Met 等位基因的年轻成年帕金森病大鼠与野生型大鼠相比表现出增强的移植功能，并且还专门出现了异常移植诱发的运动障碍 (GID) 。衰老是 PD 的主要危险因素，会降低移植物的疗效。在这里，我们研究了衰老是否与该 SNP 相互作用以进一步改变细胞移植结果。我们假设衰老会降低与这种遗传变异相关的移植物功能的增强，并加剧所有移植受试者的 GID。出乎意料的是，老年 rs6265 受试者仍保持了有益的移植功能。然而，无论基因型如何，衰老都会诱发 GID，其中在表达 rs6265 的动物中发病率和严重程度最高。