Abstract

Our laboratory now produces adeno-associated viral (AAV) vectors for gene delivery. We have obtained the reagents needed to package 7 different serotypes of AAV vectors thereby offering more selection in the type of cells/tissues that receive our transgene of interest. One use of these vectors is to delivery genes to neurons in culture. We are currently characterizing the tropism and toxicity of the various serotypes in primary neuronal cultures. These studies will establish the appropriate serotype and MOI to use to transduce our genes of interest. Using these infection parameters we can deliver various genes to in vitro models of methamphetamine-toxicity, excitotoxicity, hypoxia and Parkinson?s disease to characterize the signal transduction pathways involved in the protective and regenerative properties of bone morphogenetic proteins (BMPs). Our second approach uses AAV vectors for in vivo delivery to the brain in models of stroke, Parkinson?s disease and methamphetamine-toxicity. Specifically, we evaluate the protective and regenerative properties of BMP7 and its signaling molecules. Currently, we are testing the role of AAVBMP7 and AAVSMADs in models of Parkinson?s and methamphetamine-toxicity.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Intramural Research (Z01)
Project #
1Z01DA000443-06
Application #
7321056
Study Section
(CNL)
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2006
Total Cost
Indirect Cost

  Institution

Name
National Institute on Drug Abuse
Department
Type
DUNS #
City
State
Country
United States
Zip Code

  Publications

Li, Yazhou; Perry, TracyAnn; Kindy, Mark S et al. (2009) GLP-1 receptor stimulation preserves primary cortical and dopaminergic neurons in cellular and rodent models of stroke and Parkinsonism. Proc Natl Acad Sci U S A 106:1285-90
Chen, Yuan-Hao; Harvey, Brandon K; Hoffman, Alexander F et al. (2008) MPTP-induced deficits in striatal synaptic plasticity are prevented by glial cell line-derived neurotrophic factor expressed via an adeno-associated viral vector. FASEB J 22:261-75
Chen, Guann-Juh; Harvey, Brandon K; Shen, Hui et al. (2006) Activation of adenosine A3 receptors reduces ischemic brain injury in rodents. J Neurosci Res 84:1848-55
Woods, Amina S; Kaminski, Rafal; Oz, Murat et al. (2006) Decoy peptides that bind dynorphin noncovalently prevent NMDA receptor-mediated neurotoxicity. J Proteome Res 5:1017-23
Israelsson, Charlotte; Lewen, Anders; Kylberg, Annika et al. (2006) Genetically modified bone morphogenetic protein signalling alters traumatic brain injury-induced gene expression responses in the adult mouse. J Neurosci Res 84:47-57
Wang, Yun; Chang, Chen-Fu; Chou, Jenny et al. (2005) Dietary supplementation with blueberries, spinach, or spirulina reduces ischemic brain damage. Exp Neurol 193:75-84
Harvey, Brandon K; Hoffer, Barry J; Wang, Yun (2005) Stroke and TGF-beta proteins: glial cell line-derived neurotrophic factor and bone morphogenetic protein. Pharmacol Ther 105:113-25
Shen, Hui; Chen, Guann-Juh; Harvey, Brandon K et al. (2005) Inosine reduces ischemic brain injury in rats. Stroke 36:654-9
Harvey, B K; Chang, C F; Chiang, Y H et al. (2003) HSV amplicon delivery of glial cell line-derived neurotrophic factor is neuroprotective against ischemic injury. Exp Neurol 183:47-55
Chang, Chen-Fu; Lin, Shinn-Zong; Chiang, Yung-Hsiao et al. (2003) Intravenous administration of bone morphogenetic protein-7 after ischemia improves motor function in stroke rats. Stroke 34:558-64

Showing the most recent 10 out of 11 publications