PMID- 24523540 OWN - NLM STAT- MEDLINE DCOM- 20140402 LR - 20230701 IS - 1529-2401 (Electronic) IS - 0270-6474 (Print) IS - 0270-6474 (Linking) VI - 34 IP - 7 DP - 2014 Feb 12 TI - An adaptive role for BDNF Val66Met polymorphism in motor recovery in chronic stroke. PG - 2493-502 LID - 10.1523/JNEUROSCI.4140-13.2014 [doi] AB - 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. FAU - Qin, Luye AU - Qin L AD - Weill Cornell Medical College at Burke Medical Research Institute, White Plains, New York 10605, and Weill Cornell Medical College, New York, New York 10021. FAU - Jing, Deqiang AU - Jing D FAU - Parauda, Sarah AU - Parauda S FAU - Carmel, Jason AU - Carmel J FAU - Ratan, Rajiv R AU - Ratan RR FAU - Lee, Francis S AU - Lee FS FAU - Cho, Sunghee AU - Cho S LA - eng GR - UL1 RR024996/RR/NCRR NIH HHS/United States GR - UL1RR024996/RR/NCRR NIH HHS/United States GR - NS077897/NS/NINDS NIH HHS/United States GR - UL1 TR000457/TR/NCATS NIH HHS/United States GR - K08 NS073796/NS/NINDS NIH HHS/United States GR - R01 HL082511/HL/NHLBI NIH HHS/United States GR - NS073796/NS/NINDS NIH HHS/United States GR - R01 NS077897/NS/NINDS NIH HHS/United States GR - HL082511/HL/NHLBI NIH HHS/United States GR - P01 AG014930/AG/NIA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - J Neurosci JT - The Journal of neuroscience : the official journal of the Society for Neuroscience JID - 8102140 RN - 0 (Brain-Derived Neurotrophic Factor) SB - IM MH - Animals MH - Brain/*pathology MH - Brain-Derived Neurotrophic Factor/*genetics MH - Chronic Disease MH - Disease Models, Animal MH - Functional Laterality/*genetics MH - Gene Knock-In Techniques MH - Humans MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Motor Activity/genetics MH - *Polymorphism, Single Nucleotide MH - Real-Time Polymerase Chain Reaction MH - Recovery of Function/*genetics MH - Reverse Transcriptase Polymerase Chain Reaction MH - Stroke/complications/*genetics PMC - PMC3921423 OTO - NOTNLM OT - BDNF OT - Val66Met polymorphism OT - cerebral ischemia OT - gait OT - motor function OT - striatum EDAT- 2014/02/14 06:00 MHDA- 2014/04/03 06:00 PMCR- 2014/02/12 CRDT- 2014/02/14 06:00 PHST- 2014/02/14 06:00 [entrez] PHST- 2014/02/14 06:00 [pubmed] PHST- 2014/04/03 06:00 [medline] PHST- 2014/02/12 00:00 [pmc-release] AID - 34/7/2493 [pii] AID - 4140-13 [pii] AID - 10.1523/JNEUROSCI.4140-13.2014 [doi] PST - ppublish SO - J Neurosci. 2014 Feb 12;34(7):2493-502. doi: 10.1523/JNEUROSCI.4140-13.2014.