Advancing Age and the rs6265 BDNF SNP are Permissive to Graft-induced Dyskinesias in Parkinsonian Rats

TL;DR

This study shows that aging and a specific genetic variant increase the risk of movement disorders after cell transplants in Parkinson's disease models.

Contribution

The study reveals that aging interacts with the rs6265 BDNF SNP to worsen graft-induced dyskinesias in Parkinsonian rats.

Findings

Aged rs6265 rats maintained improved graft function despite aging.

Aging increased the likelihood of graft-induced dyskinesias in all genotypes.

The highest dyskinesia severity occurred in aged rs6265 rats.

Abstract

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 dampen 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.