Brain microsomal calcium accumulation in rats with increasing age: involvement of thapsigargin-sensitive Ca2+-ATPase.

The alteration in calcium content and Ca2+-ATPase activity in the brain microsomes of rats with increasing age was investigated. Brain microsomal calcium content was significantly increased in aged rats (50 weeks old) as compared with that of young rats (5 weeks old). Such an increase was not seen in the brain mitochondria of aged rats. Increasing age caused a significant elevation of Ca2+-ATPase activity in the brain microsomes. The microsomal Ca2+-ATPase activity of young rats was significantly decreased by the addition of thapsigargin (10-7-10-5 M), a specific inhibitor of microsomal Ca2+ pump enzyme (Ca2+-ATPase), in the enzyme reaction mixture. The inhibitory effect of thapsigargin (10-5 M) was also seen in the brain microsomes of aged rats. Moreover, the effect of calcium (5 and 10 microM) addition in elevating Ca2+-ATPase activity was not revealed in the microsomes of aged rats, whereas the metal could increase the enzyme activity in young rats, suggesting an involvement of activatory factor on the enzyme with increasing age. The present study demonstrates that ageing induces an increase in thapsigargin-sensitive Ca2+-ATPase activity and a corresponding elevation of calcium content in the brain microsomes. This finding suggests a cellular mechanism by which ageing causes calcium accumulation in brain.