Impaired calcium homeostasis in aged hippocampal neurons

Development of neurodegenerative diseases such as Alzheimer's and Parkinson's disease is strongly age-associated. The impairment of calcium homeostasis is considered to be a key pathological event leading to neuronal dysfunction and cell death. However, the exact impact of aging on calcium homeostasis in neurons remains largely unknown. In the present work we have investigated intracellular calcium levels in cultured primary hippocampal neurons from young (2 months) and aged (24 months) rat brains. Upon stimulation with glutamate or hydrogen peroxide aged neurons in comparison to young neurons demonstrated an increased vulnerability to these disease-related toxins. Measurement of calpain activity using Western blot analysis showed a significant increase in basal activity of calpains in aged neurons. The observed increase of calpain activity was correlated with elevated protein levels of μ-calpain. Ca2+-imaging experiments performed on living individual neurons using the dye calcium green demonstrated a twofold increase in intracellular calcium concentration in aged neurons as compared to young neurons. The observed changes of intracellular calcium in aged neurons might play a role in their increased vulnerability to neurodegeneration.