Elsevier

Brain Research

Volume 842, Issue 1, 18 September 1999, Pages 224-229
Brain Research

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

https://doi.org/10.1016/S0006-8993(99)01827-2Get rights and content

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 PS1 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.

Section snippets

Acknowledgements

This work was supported by grants to M.P.M. from the NIA and NINDS.

References (49)

  • N. Pitsikas et al.

    Deterioration of spatial and nonspatial reference and working memory in aged rats: protective effect of life-long calorie restriction

    Neurobiol. Aging

    (1992)
  • R.S. Sohal et al.

    Oxidative damage, mitochondrial oxidant generation and antioxidant defenses during aging and in response to food restriction in the mouse

    Mech. Ageing Dev.

    (1994)
  • J. Stewart et al.

    The effects of life-long food restriction on spatial memory in young and aged Fischer 344 rats measured in the eight-arm radial and the Morris water mazes

    Neurobiol. Aging

    (1989)
  • R.L. Weindruch et al.

    The retardation of aging by dietary restriction: longevity, immunity and lifetime energy intake

    J. Nutr.

    (1986)
  • Z.F. Yu et al.

    The endoplasmic reticulum stress-responsive protein GRP78 protects neurons against excitotoxicity and apoptosis: suppression of oxidative stress and stabilization of calcium homeostasis

    Exp. Neurol.

    (1999)
  • J.G. Begley et al.

    Altered calcium homeostasis and mitochondrial dysfunction in cortical synaptic compartments of presenilin-1 mutant mice

    J. Neurochem.

    (1999)
  • A.J. Bruce-Keller et al.

    4-Hydroxynonenal, a product of lipid peroxidation, damages cholinergic neurons and impairs visuospatial memory in rats

    J. Neuropathol. Exp. Neurol.

    (1998)
  • A.J. Bruce-Keller et al.

    Food restriction reduces brain damage and improves behavioral outcome following excitotoxic and metabolic insults

    Ann. Neurol.

    (1999)
  • W. Duan et al.

    Dietary restriction and 2-deoxyglucose administration improve behavioral outcome and reduce degeneration of dopaminergic neurons in models of Parkinson's disease

    J. Neurosci. Res.

    (1999)
  • K. Duff et al.

    Increased amyloid-β42(43) in brains of mice expressing mutant presenilin 1

    Nature

    (1996)
  • J.A. Ehrenfried et al.

    Caloric restriction increases the expression of heat shock protein in the gut

    Ann. Surg.

    (1996)
  • C.E Finch, T.E. Morgan, Food restriction and brain aging, in: M.P. Mattson, J.W. Geddes (Eds.), The Aging Brain, JAI...
  • P.F. Good et al.

    Evidence of neuronal oxidative damage in Alzheimer's disease

    Am. J. Pathol.

    (1996)
  • Q. Guo et al.

    Alzheimer's PS-1 mutation perturbs calcium homeostasis and sensitizes PC12 cells to death induced by amyloid β-peptide

    NeuroReport

    (1996)
  • Cited by (0)

    View full text