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The effects of aging and neurodegeneration on apoptosis-associated DNA fragmentation and the benefits of nicotinamide

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Molecular and Chemical Neuropathology

Abstract

In this work, the tertiary butylhydroperoxide-(t-BuOOH) treated mouse was used as a model to study the oxidative stress that is associated with various neurodegenerative diseases. DNA was found to be an early target oft-BuOOH attack. Necrosis was associated with extensive DNA fragmentation that occurred in almost all regions of the brain within 20 min following intracerebroventricular (icv) injection of 109.7 mg/kgt-BuOOH. Apoptosis was associated with high levels of DNA fragmentation that was observed at 48 h after icv administration of 21.9 mg/kgt-BuOOH. Susceptibility to DNA damage was found to be age-dependent, since 24-mo-old mice exhibited consistently higher and more pervasive DNA damage than 8 mo-old-mice. Extensive DNA damage was seen in various brain regions in patients with Alzheimer disease (AD) and with both Alzheimer and Parkinson disease (AD-PD). These results directly implicate DNA damage in neurodegeneration. The DNA fragmentation ob-served can lead to both apoptosis and necrosis, as suggested by gel electrophoresis. Nicotinamide, a precursor of NAD in the brain, was able to prevent DNA fragmentation induced by low-doset-BuOOH, when coadministered with the toxin.

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Authors and Affiliations

  1. School of Pharmacy, Department of Molecular Pharmacology and Toxicology, University of Southern California, 1985 Zonal Avenue, PSC 508, 90033, Los Angeles, CA

    Suman K. Mukherjee & James D. Adams

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  1. Suman K. Mukherjee
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  2. James D. Adams
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Correspondence to James D. Adams.

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Mukherjee, S.K., Adams, J.D. The effects of aging and neurodegeneration on apoptosis-associated DNA fragmentation and the benefits of nicotinamide. Molecular and Chemical Neuropathology 32, 59–74 (1997). https://doi.org/10.1007/BF02815167

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  • DOI: https://doi.org/10.1007/BF02815167

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