Calcium as sculptor and destroyer of neural circuitry

Mark P. Mattson

Research output: Contribution to journalArticlepeer-review

Abstract

This paper examines the hypothesis that intracellular calcium plays guiding roles in the formation and adaptive modification of neural circuits in development and adult plasticity and that imbalances in calcium regulation lead to the degeneration of neural circuits in aging and disease. The neuronal growth cone is the motile structure largely responsible for the generation of neuroarchitecture. Studies of developing neurons in culture demonstrated that environmental signals believed to play key roles in neural development (i.e., neurotransmitters and growth factors) regulate growth cones by altering neuronal calcium-regulating systems. Different components of neurite outgrowth (i.e., neurite elongation and growth cone motility) are based upon different cytoskeletal systems (microtubules and microfilaments) which are differentially affected by calcium. In addition, cytoskeleton-associated proteins such as tau and microtubule-associated protein 2 (MAP2) are likely candidates for regulation by calcium. "Natural" neuronal death in development may occur as the result of growth factor deficiency or excess excitatory activity leading to sustained elevations in intracellular calcium levels. With aging and in disease, a loss of calcium homeostasis may underlie the aberrant neurodegeneration that occurs. For example, neurons subjected to conditions (e.g., glutamate and β-amyloid) that cause sustained rises in intracellular calcium exhibit changes in the cytoskeleton similar to those seen in neurofibrillary tangles of Alzheimer's disease and related disorders. Taken together, the data suggest that cellular systems for calcium homeostasis are integral to both the adaptive and aberrant neuroarchitectural changes that occur throughout the lifespan of the nervous system.

Original languageEnglish (US)
Pages (from-to)29-49
Number of pages21
JournalExperimental Gerontology
Volume27
Issue number1
DOIs
StatePublished - 1992
Externally publishedYes

ASJC Scopus subject areas

  • Aging
  • Medicine(all)

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