Primary mechanism responsible for age-dependent neuronal dehydration

Neuronal dehydration and high [Ca 2+ ] i are essential hallmarks for age-dependent memory impairment. Na + /K + -ATPase, having membrane transporting and intracellular signaling functions, has age-induced dysfunctional character. Therefore, it could have a key role in age-dependent neuronal dehydration and increase of [Ca 2+ ] i . However, it is not clear the dysfunction of which above mentioned functions of Na + /K + -ATPase serves as a primary mechanism for generation of age-dependent neuronal dehydration and increase of [Ca 2+ ] i . In present work age-dependent effects of ≤10 -9 M (agonist for α 3 isoform which has only signaling function) and 10 -4 M ouabain (agonist for α 1 isoform which has ion-transporting function) on brain cortex tissue hydration, 45 Ca 2+ uptake and 45 Ca 2+ efflux through plasma membrane were studied. It was shown that ≤10 -9 M and 10 -4 M ouabain concentrations have stimulation effects on cortex tissue hydration and Na + /Ca 2+ exchange in reverse mode. However, these effects have age-dependent weakening and increasing characters, respectively. It is suggested that ≤10 -9 M ouabain-induced tissue hydration is due to cAMP-activated Ca 2+ -ATPase in endoplasmic reticulum membrane leading to reversion of Na + /Ca 2+ exchange and elevation of endogenous H 2 O release in cytoplasm. This effect has age-dependent depressing character. Thus, the dysfunction of α 3 isoform-dependent intracellular signaling system could be considered as a primary mechanism for age-dependent neuronal dehydration.