Accession Number:

ADA383050

Title:

Mechanisms of Neuronal Apoptosis In Vivo

Descriptive Note:

Annual rept. 1 Jul 1999-30 Jun 2000

Corporate Author:

JOHNS HOPKINS UNIV BALTIMORE MD

Personal Author(s):

Report Date:

2000-07-01

Pagination or Media Count:

263.0

Abstract:

Understanding the mechanisms of neuronal apoptosis in the central nervous system CNS has broad significance for military personnel and civilians. Neuronal apoptosis can occur after exposure to neurotoxins, radiation, and viruses and as a result of seizure activity, trauma, limb amputation, and hypoxia-ischemia caused by cardiac arrest, stroke, and increased intracranial pressure. The goal of this research project is to identify mechanisms of neuronal apoptosis. During the first year of funding, we found that neuronal apoptosis in the adult CNS occurs in association with activation of the oncosuppressor protein p53 and caspase-3. Furthermore, we discovered that neuronal apoptosis in the CNS is mediated by both p53-dependent and p53-independent cell death pathways and requires the programmed cell death protein Bax. In the immature brain, neuronal apoptosis is preceded by elevated levels of the cell membrane death receptor Fas and Bax, abnormalities in mitochondria, and activation of caspase-8 and caspase-3. Thus, the in vivo mechanisms for neuronal apoptosis in the adult and immature CNS may be dissimilar. We also employed a new technique single-cell gel electrophoresis to study mechanisms of neuronal apoptosis. We identified oxidative stress-induced, DNA single-strand breaks as a possible early upstream signal for neuronal apoptosis.

Subject Categories:

  • Anatomy and Physiology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE