Accession Number:

ADA434706

Title:

Neurotrophin Therapy of Neurodegenerative Disorders with Mitochondrial Dysfunction

Descriptive Note:

Annual rept. 1 Sep 2003-31 Aug 2004

Corporate Author:

MARYLAND UNIV BALTIMORE

Personal Author(s):

Report Date:

2004-09-01

Pagination or Media Count:

11.0

Abstract:

This research program will determine whether accelerated neuron death due to increased oxidative stress resulting from mitochondrial dysfunction can be compensated or corrected by neurotrophin stimulation. The experiments will be carried out in two models of mitochondrial dysfunction. 1hippocampal neurons from the trisomy 16 mouse, which undergo increased apoptosis and have a mitochondrial defect, that has now been identified as a decrease in Complex I-mediated respiration and 2neurons chronically treated with the neurotoxin rotenone to induce a defect in mitochondrial function. 0.1-0.5 nM rotenone treatment has now been shown to leave hippocampal neurons vulnerable to a second oxidative stress. A unique aspect of this approach is that the neuronal responsiveness to brain derived neurotrophic factor BDNF will be enhanced by overexpressing the BDNF receptor via an andenovirus vector, resulting in an increase in sensitivity to BDNF. Such neurons would be expected to have an enhanced survival response to endogenous BDNF and may be more resistant to oxidative stress characteristic of Parkinsons disease and other neurodegenerative disorders.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE