Neuroprotective effect of selenium in rats subjected to chronic intermittent cold and immobilization stress: The role of phosphorylated tau.

OBJECTIVES

The current study aimed to investigate the potential neuroprotective effect of selenium against cognitive dysfunction in rats subjected to chronic intermittent stress.

MATERIALS AND

METHODS

Ninety adult male Wistar rats were randomly assigned into five groups (n=18): (1) N: non-stressed group; (2) CS: cold-stressed non-treated group; (3) IS: immobilized-stressed non-treated group; (4) CS/Se: cold-stressed/ selenium-treated group; and (5) IS/Se: immobilized-stressed/selenium-treated group. Memory and learning were assessed using the Morris Water Maze, novel object recognition, and Y-maze tests. After completion of neurobehavioral tests, fasting retro-orbital blood samples were collected from all rats. Stress hormones, serum sodium and potassium, oxidative stress markers (malondialdehyde (MDA), total antioxidant capacity (TAC), glutathione peroxidase (GPx), and thioredoxin reductase (TrxR)), and the proinflammatory markers (tumor necrosis factor-alpha (TNF-α), intercellular adhesion molecule-1 (ICAM-1)) were measured. Histopathological examination of the hippocampus and immunohistochemistry of p-tau were performed.

RESULTS

The results indicated that memory and learning were impaired by chronic intermittent stress. This was associated with histopathological changes of the hippocampus and increased the expression of p-tau. Selenium administration improved the cognitive dysfunction as indicated by behavioral tests. Also, it reduced the levels of stress hormones, sodium, MDA, and the proinflammatory markers. It significantly enhanced the antioxidant enzyme activities and increased the potassium level. In addition, it improved the histopathological changes of the hippocampus and decreased the expression of p-tau.

CONCLUSION

Coadministration of selenium to rats subjected to chronic stress improved cognitive dysfunction by its antioxidant and anti-inflammatory effects, as well as via downr-egulation of p-tau in the hippocampus.