title: An adaptive role for BDNF Val66Met polymorphism in motor recovery in chronic stroke.
abstract: Little is known about the influence of genetic diversity on stroke recovery. One exception is the polymorphism in brain derived neurotrophic factor (BDNF), a critical neurotrophin for brain repair and plasticity. Humans have a high-frequency single nucleotide polymorphism (SNP) in the prodomain of the BDNF gene. Previous studies show that the BDNF Val66Met variant negatively affects motor learning and severity of acute stroke. To investigate the impact of this common BDNF SNP on stroke recovery, we used a mouse model that contains the human BDNF Val66Met variant in both alleles (BDNF(M/M)). Male BDNF(+/+) and BDNF(M/M) littermates received sham or transient middle cerebral artery occlusion. We assessed motor function regularly for 6 months after stroke and then performed anatomical analyses. Despite reported negative association of the SNP with motor learning and acute deficits, we unexpectedly found that BDNF(M/M) mice displayed significantly enhanced motor/kinematic performance in the chronic phase of motor recovery, especially in ipsilesional hindlimb. The enhanced recovery was associated with significant increases in striatum volume, dendritic arbor, and elevated excitatory synaptic markers in the contralesional striatum. Transient inactivation of the contralateral striatum during recovery transiently abolished the enhanced function. This study showed an unexpected benefit of the BDNFVal66Met carriers for functional recovery, involving structural and molecular plasticity in the nonstroked hemisphere. Clinically, this study suggests a role for BDNF genotype in predicting stroke recovery and identifies a novel systems-level mechanism for enhanced motor recovery.
authors: Weill Cornell Medical College at Burke Medical Research Institute, White Plains, New York 10605, and Weill Cornell Medical College, New York, New York 10021.
authors: Luye
authors: L
authors: Qin
authors: Deqiang
authors: D
authors: Jing
authors: Sarah
authors: S
authors: Parauda
authors: Jason
authors: J
authors: Carmel
authors: Rajiv R
authors: RR
authors: Ratan
authors: Francis S
authors: FS
authors: Lee
authors: Sunghee
authors: S
authors: Cho
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D002908:Chronic Disease; D004195:Disease Models, Animal; D007839:Functional Laterality / Q000235:genetics*; D055879:Gene Knock-In Techniques; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D060888:Real-Time Polymerase Chain Reaction; D020127:Recovery of Function / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020521:Stroke / Q000150:complications / Q000235:genetics*
chemical_list: D019208:Brain-Derived Neurotrophic Factor
keywords: BDNF; Val66Met polymorphism; cerebral ischemia; gait; motor function; striatum