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Age-related decrease in brain synaptic membrane Ca2+-ATPase in F344/BNF1 rats

A Zaidi1, J Gao, T C Squier

  • 1Department of Pharmacology and Toxicology, University of Kansas, Lawrence 66045, USA.

Neurobiology of Aging
|January 8, 1999
PubMed
Summary
This summary is machine-generated.

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Brain synaptic plasma membrane Ca2+-ATPase activity declines with age in hybrid rats. This age-related decrease in plasma membrane Ca2+-ATPase (PMCA) activity is linked to reduced PMCA levels and altered calmodulin function.

Area of Science:

  • Neuroscience
  • Biochemistry
  • Gerontology

Background:

  • Age-related cognitive decline is a significant concern.
  • Plasma membrane Ca2+-ATPase (PMCA) is crucial for maintaining calcium homeostasis in neurons.
  • Previous studies indicated reduced PMCA activity in aged inbred rats.

Purpose of the Study:

  • To investigate age-dependent changes in brain synaptic plasma membrane (SPM) Ca2+-ATPase activity in F344/BNF1 hybrid rats.
  • To determine if reduced PMCA activity observed in inbred rats extends to their hybrids.
  • To explore the underlying mechanisms, including PMCA protein levels and calmodulin (CaM) interactions.

Main Methods:

  • Utilized Fisher 344/Brown Norway hybrid rats (F344/BNF1) across different age groups.
  • Measured SPM Ca2+-ATPase activity (Vmax and K(act) for Ca2+) in brain tissue.

Related Experiment Videos

  • Quantified immunoreactive PMCA levels using Western blotting or similar techniques.
  • Assessed CaM binding to membranes and its stimulatory effectiveness on PMCA activity.

    • Main Results:

    • A progressive, age-dependent decrease in Vmax of SPM Ca2+-ATPase activity was observed in F344/BNF1 rats.
    • PMCA protein levels in SPMs decreased by approximately 20% in aged rats.
    • CaM bound to membranes and its ability to stimulate PMCA activity were reduced in older rats, potentially due to age-related structural changes or oxidation.

    Conclusions:

    • PMCA activity in SPMs of F344/BNF1 hybrid rats decreases with age.
    • The reduction in PMCA activity is partly due to a loss of PMCA protein from the membrane.
    • Age-related alterations in calmodulin structure may impair its interaction with SPMs, contributing to decreased PMCA function.