Dietary restriction protects hippocampal neurons against the death- promoting action of a presenilin-1 mutation

Haiyan Zhu, Qing Guo, Mark P. Mattson

Research output: Contribution to journalArticle

Abstract

Alzheimer's disease (AD) is an age-related disorder that involves degeneration of synapses and neurons in brain regions involved in learning and memory processes. Some cases of AD are caused by mutations in presenilin- 1 (PS1), an integral membrane protein located in the endoplasmic reticulum. Previous studies have shown that PSi mutations increase neuronal vulnerability to excitotoxicity and apoptosis. Although dietary restriction (DR) can increase lifespan and reduce the incidence of several age-related diseases in rodents, the possibility that DR can modify the pathogenic actions of mutations that cause AD has not been examined. The vulnerability of hippocampal neurons to excitotoxic injury was increased in PS1 mutant knockin mice. PS1 mutant knockin mice and wild-type mice maintained on a DR regimen for 3 months exhibited reduced excitotoxic damage to hippocampal CA1 and CA3 neurons compared to mice fed ad libitum; the DR regimen completely counteracted the endangering effect of the PS1 mutation. The magnitude of increase in levels of the lipid peroxidation product 4-hydroxynonenal following the excitotoxic insult was lower in DR mice compared to mice fed ad libitum, suggesting that suppression of oxidative stress may be one mechanism underlying the neuroprotective effect of DR. These findings indicate that the neurodegeneration-promoting effect of an AD-linked mutation is subject to modification by diet.

Original languageEnglish (US)
Pages (from-to)224-229
Number of pages6
JournalBrain Research
Volume842
Issue number1
DOIs
StatePublished - Sep 18 1999
Externally publishedYes

Fingerprint

Presenilin-1
Neurons
Mutation
Alzheimer Disease
Rodent Diseases
Diet Therapy
Nerve Degeneration
Neuroprotective Agents
Endoplasmic Reticulum
Synapses
Lipid Peroxidation
Membrane Proteins
Oxidative Stress
Learning
Apoptosis
Incidence
Wounds and Injuries
Brain

Keywords

  • Alzheimer
  • Apoptosis
  • Calorie restriction
  • Excitotoxicity
  • Hyroxynonenal
  • Kainate
  • Oxidative stress

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Dietary restriction protects hippocampal neurons against the death- promoting action of a presenilin-1 mutation. / Zhu, Haiyan; Guo, Qing; Mattson, Mark P.

In: Brain Research, Vol. 842, No. 1, 18.09.1999, p. 224-229.

Research output: Contribution to journalArticle

Zhu, Haiyan ; Guo, Qing ; Mattson, Mark P. / Dietary restriction protects hippocampal neurons against the death- promoting action of a presenilin-1 mutation. In: Brain Research. 1999 ; Vol. 842, No. 1. pp. 224-229.
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