Parameters of calcium homeostasis in normal neuronal ageing

Abstract

The last decade has witnessed a significant turn in our understanding of the mechanisms responsible for the decline of cognitive functions in aged brain. As has been demonstrated by detailed morphological reassessments, the senescence-related changes in cognition cannot be attributed to a simple decrease in the number of neurons. It is becoming clearer that a major cause of age-induced deterioration of brain capability involves much subtler changes at the level of synapses. These changes are either morphological, i.e. reduction in the number of effective synapses and/or functional alterations, i.e. changes in the efficacy of remaining synapses. Important questions are now raised regarding the mechanisms which mediate these synaptic changes. Clearly, an important candidate is calcium, the cytotoxic role of which is already firmly established. The wealth of evidence collected so far regarding the changes of Ca²⁺ homeostasis in aged neurons shows that the overall duration of cytoplasmic Ca²⁺ signals becomes longer. This is the most consistent result, demonstrated on different preparations and using different techniques. What is not yet clear is the underlying mechanism, as this result could be explained either through an increased Ca²⁺ influx or because of a deficit in the Ca²⁺ buffering/clearance systems. It is conceivable that these prolonged Ca²⁺ signals may exert a local excitotoxic effect, removing preferentially the most active synapses. Uncovering of the role of Ca²⁺ in the synaptic function of the aged brain presents an exciting challenge for all those involved in the neurobiology of the senescent CNS.