Endocrine Abstracts

Introduction: There is evidence that chronic mild hyponatremia (serum (Na+) 130–135 mmol/l) may have clinical consequences, such as fracture occurrence and neurological symptoms including unsteadiness, falls and attention deficits. These have been traditionally associated to water movement into nervous cells, as a result of the hypotonic state. The aim of the present study was to determine whether low extracellular sodium directly exerts negative effects on human neuronal cells, independent of reduced osmolality.

Design: We exposed two neuronal cell models (i.e. SK-N-AS and SH-SY5Y neuroblastoma cell lines) to sustained low extracellular sodium, thus mimicking a condition of chronic hyponatremia, both in the presence of reduced or unaltered osmolality, obtained with the addition of appropriate amounts of mannitol.

Results: We found that very low sodium (i.e. 115 and 90 mmol/l in SK-N-AS and SH-SY5Y, respectively) significantly reduced cell viability and adhesion. However, intermediate low sodium was able to cause cell distress, as assessed by the altered expression of anti-apoptotic genes and the reduced ability to differentiate into a mature neuronal phenotype. Noteworthy, these effects were observed also in the presence of unaltered osmolality. Moreover, we performed a comprehensive micro-array analysis in cells maintained in normal sodium or in low sodium and unaltered osmolality and we found that the most altered pathway included genes involved in ‘cell death and survival’. Among the 43 differentially expressed genes, the Heme oxigenase gene, which represents a transcriptional response to oxidative stress, showed the highest increase in the expression level.

Conclusions: This study demonstrates that low extracellular (Na+) directly cause detrimental effects in neuronal cells independent of reduced osmolality. These findings further support the recommendation to effectively correct hyponatremia, even when mild and chronic.