Neuronal vulnerability and degeneration-life and death in the aging brain

John Morrison, Patrick R. Hof

Research output: Contribution to journalArticle

Abstract

While age is clearly an important risk factor for neurodegenerative disorders involving neuron death, recent data suggest that neuron death is not widespread in normal aging. For example, in the case of Alzheimer's disease (AD), the most vulnerable circuits in the cerebral cortex are the perforant path interconnecting entorhinal cortex and hippocampus, and the long corticocortical circuits interconnecting association cortices, and these circuits share key attributes that may be linked to their selective vulnerability. However, these links to selective vulnerability for neuron death may not be as relevant to many of the processes occurring in normal aging that lead to age-related functional decline. For example, while the perforant path is exceedingly vulnerable to degeneration in AD, data from human and aged monkeys demonstrate that it does not degenerate in normal aging, nor do the neurons in the entorhinal cortex that provide this projection decline in number. However, while this circuit is structurally intact in normal aging, it is not unaffected. Aged monkeys exhibit a circuit-specific alteration in NMDA receptor levels in the perforant path terminal zone. NMDA receptors are also responsive to changes in circulating estrogen levels and in fact, estrogen replacement therapy has been demonstrated to upregulate NMDA receptors in CA1 and dentate gyrus, without any effect in CA3. Such circuit and region-specific changes in NMDA receptors likely have profound implications for memory processes, even though they occur in the absence of neuron death.

Original languageEnglish (US)
JournalFASEB Journal
Volume12
Issue number5
StatePublished - Mar 20 1998
Externally publishedYes

Fingerprint

Brain
Perforant Pathway
N-Methyl-D-Aspartate Receptors
Aging of materials
neurons
Neurons
death
brain
Networks (circuits)
cortex
Entorhinal Cortex
receptors
Alzheimer disease
Haplorhini
monkeys
Alzheimer Disease
estrogen replacement therapy
Estrogens
Estrogen Replacement Therapy
cerebral cortex

ASJC Scopus subject areas

  • Agricultural and Biological Sciences (miscellaneous)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Cell Biology

Cite this

Neuronal vulnerability and degeneration-life and death in the aging brain. / Morrison, John; Hof, Patrick R.

In: FASEB Journal, Vol. 12, No. 5, 20.03.1998.

Research output: Contribution to journalArticle

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