Primary mechanism responsible for age-dependent neuronal dehydration

Abstract

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