Endocrine Abstracts

Hyponatraemia is the most frequent electrolyte disorder encountered in hospitalized patients. Hyponatraemia causes a wide variety of neurological signs and symptoms, depending on the rate and degree of serum sodium drop. The negative effects of low extracellular sodium concentrations ((Na+)) on neuronal cells are known to be due to the entry of fluids into the cells, as a consequence of reduced plasma osmolality. To date, it has not been investigated whether low (Na+) have direct effects on neuronal cells. To this purpose, by generating media with physiological or low (131, 127, 121, 115, 100 and 90 mM; Na+), we studied whether low (Na+) are able per se to cause negative biological effects in two different neuronal cell lines (SK-N-AS and SH-SY5Y). We evaluated cell viability and adhesion after adapting to and maintaining cells in culture for 7 days at target (Na+) media. Results showed a significant decrease in cell viability starting from 115 mM (Na+) for SK-N-AS (49.6±1% vs control) and from 90 mM (Na+) for SH-SY5Y (22±0.4% vs control). Cell adhesion was also decreased vs control cells (SK-N-AS 58±0.7%; SH-SY5Y 48.7±2%). Similar results were obtained also when the reduced osmolality due to low (Na+) were corrected by adding mannitol. Moreover, we observed a downregulation of the expression of antiapoptotic genes (bcl2, mdm2) and of the neuroprotective gene DHCR24 at the same reduced (Na+). Finally, by using electrophysiological techniques, we observed that 115 mM (Na+) for SK-N-AS and 90 mM (Na+) for SH-SY5Y significantly shifted the reversal potential towards more negative voltages, also when osmolality was corrected. This result could be mainly ascribed to a decrease of intracellular (Ca²⁺) possibly involving Ca²⁺ and Na/K pumps and could lead to a reduced cell response in hyponatraemic conditions. In summary, these findings show for the first time that low (Na+) directly cause detrimental effects on neuronal cells, independent of extracellular osmolality.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This work was supported, however funding details unavailable.