An Adaptive Role for BDNF Val66Met Polymorphism in Motor Recovery in Chronic Stroke

• DOI: 10.1523/jneurosci.4140-13.2014
• Publication Date: 2014-02-12T17:28:13Z
• Authors: Luye Qin; Deqiang Jing; Sarah Parauda; Jason Carmel; Rajiv R. Ratan; Francis S. Lee; Sunghee Cho
• Keywords: Chronic stroke; Stroke

Little is known about the influence of genetic diversity on stroke recovery. One exception polymorphism in brain derived neurotrophic factor (BDNF), a critical neurotrophin for repair and plasticity. Humans have high-frequency single nucleotide (SNP) prodomain BDNF gene. Previous studies show that Val66Met variant negatively affects motor learning severity acute stroke. To investigate impact this common SNP recovery, we used mouse model contains human both alleles (BDNF(M/M)). Male BDNF(+/+) BDNF(M/M) littermates received sham or transient middle cerebral artery occlusion. We assessed function regularly 6 months after then performed anatomical analyses. Despite reported negative association with deficits, unexpectedly found mice displayed significantly enhanced motor/kinematic performance chronic phase especially ipsilesional hindlimb. The recovery was associated significant increases striatum volume, dendritic arbor, elevated excitatory synaptic markers contralesional striatum. Transient inactivation contralateral during transiently abolished function. This study showed an unexpected benefit BDNFVal66Met carriers functional involving structural molecular plasticity nonstroked hemisphere. Clinically, suggests role genotype predicting identifies novel systems-level mechanism