Abstract:

Change in “calcium homeostasis” is one of the mechanisms that proposed to expl ain the age-dependent injuries of neurons. But what is the most reliable age-a ssociated changes in neuronal Ca²⁺ homeostasis, and are these changes prim ary or secondary to other changes in the physiology of the aged neurons? Here we used the most physiological in vitro preparation-the parasagittal cerebellar slices, obtained from animals of different ages (11-23 months)-to perform sim ultaneous measurements of both intracellular calcium ([Ca²⁺]_i) and mit ochondrial membrane potential (MMP) in real time. A 15-second pulse of glutamat e, kainic acid (KA) or N-methyl-D-aspartic acid (NMDA) was used to trigger a calcium signal. No changes were found on the mean resting [Ca²⁺]_i values of aged neurons, while the MMP already sho wed a significant decrease. Most of the changes in the calcium homeostasis appea red only when the aged neurons were exposed to higher levels of stimulation and the most significant change was the decreased recovery rate of calcium signal, t ogether with a delayed recovery of MMP. The close and significant (P< 0.00 1) correlation between the status of neuronal mitochondria and [Ca²⁺]_i 1 minute after the remove of stimulation indicated that the changes of calcium ho meostasis were secondary to the impairment of mitochondrial function.