Decrease in Ca2+-ATPase activity in the brain plasma membrane of rats with increasing age: involvement of brain calcium accumulation

The alteration in Ca(2+)-ATPase activity in the brain plasma membrane of rats with increasing age was investigated. Calcium content in the brain tissues was significantly raised in aged rats (50 weeks old) as compared with that of young rats (5 weeks old). Increasing age caused a significant decrease in Ca(2+)-ATPase activity in the brain plasma membranes. The presence of N-ethylmaleimide (2.5 or 5 mM), a modifying reagent of thiol (SH)-groups, in the reaction mixture caused a significant decrease in the brain plasma membrane Ca(2+)-ATPase activity of young and aged rats, while dithiothreitol (2.5 or 5 mM), a protecting reagent of SH-groups, produced a significant increase in the enzyme activity, indicating that the SH-group is an active site of Ca(2+)-ATPase. The active site of Ca(2+)-ATPase may not be impaired by ageing. The brain plasma membrane Ca(2+)-ATPase activity of young rats was significantly reduced in the presence of dibutyryl cyclic AMP (10(-7)-10(-5) M) or inositol 1, 4, 5-trisphosphate (10(-7)-10(-5) M) in the reaction mixture. Such an decrease was not seen in aged rats. The responsibility for signaling factors seemed to be weakened by ageing. Calmodulin (2.5 and 5 microg/ml) or regucalcin (10(-8) and 10(-7) M), a Ca(2+)-regulating protein, did not have an effect on Ca(2+)-ATPase activity. This study demonstrates that ageing induces a decrease in Ca(2+)-ATPase activity in the brain plasma membranes. This finding suggests a cellular mechanism by which ageing causes calcium accumulation in brain.