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Impact of BDNF SNP on Stroke-Induced Plasticity and Motor Function

September 15, 2012 to May 31, 2017
GRANT: 
Federal
Funding Status: 
Completed Project
Funding Agency: 
National Institutes of Health (NIH)
Funding Institute: 
National Institute of Neurological Disorders and Stroke (NINDS)
Grant Number: 
R01NS077897
Published Grant: 
NIH RePORT

Goals

  • Aim 1 will test the hypothesis that the BDNFMet allele promotes motor recovery via effects in the contralateral striatum. Using WT, BDNF+/Met, and BDNFMet/Met mice subjected to ischemic stroke, we will assess motor functions, analyze sub-region volume, and address the importance of the contralateral striatum by assessing behavior changes after acute pharmacological inactivation of the contralateral striatum.
  • Aim 2 will test the hypothesis that the BDNFMet allele induces synaptic changes and shifts synaptic balance to an excitatory status in the striatum. Detailed neuronal morphology and changes in synaptic properties will be investigated. We have shown that BDNFMet/Met mice display increased expression of the inflammatory receptor CD36, which functions in innate immunity and wound healing, and also of its ligand thrombospondins (TSPs) that are involved in the formation of excitatory synapses. We will therefore test the hypothesis that the CD36 pathway contributes to BDNFMet allele-induced synaptic plasticity and motor recovery through synaptic excitation in the contralateral striatum in Aim 3. CD36, TSPs, excitatory and inhibitory synaptic markers will be assessed in WT and BDNFMet/Met mice following stroke. The importance of CD36 in BDNFMet allele-induced brain plasticity will be addressed in BDNFMet/Met mice that lack CD36 or in mice that have been treated with a CD36 antagonist.

The insight gained from the studies will provide a means to predict the course of stroke recovery relevant to BDNF SNP carriers. In addition, defining a critical window for activating the CD36 pathway may lead to therapeutic strategies for promoting motor recovery in stroke patients who do not carry the SNP.

Investigators

Sunghee's Photo
Lab Director
Stroke Neuroimmunology Laboratory
Role: 
Principal Investigator

Associated

Conditions & Recovery

Motor Recovery Icon
Write and walk again.
Stroke icon
Stroke is the leading cause of disability in the U.S.

Research Methods