Supplementation with Vitamin D 3 Protects against Mitochondrial Dysfunction and Loss of BDNF-Mediated Akt Activity in the Hippocampus during Long-Term Dexamethasone Treatment in Rats.

Dexamethasone (DEXA) is a commonly used steroid drug with immunosuppressive and analgesic properties. Unfortunately, long-term exposure to DEXA severely impairs brain function. This study aimed to investigate the effects of vitamin D 3 supplementation during chronic DEXA treatment on neurogenesis, mitochondrial energy metabolism, protein levels involved in the BDNF-mediated Akt activity, and specific receptors in the hippocampus. We found reduced serum concentrations of 25-hydroxyvitamin D 3 (25(OH)D 3 ), downregulated proBDNF and pAkt, dysregulated glucocorticosteroid and mineralocorticoid receptors, impaired mitochondrial biogenesis, and dysfunctional mitochondria energy metabolism in the DEXA-treated group. In contrast, supplementation with vitamin D 3 restored the 25(OH)D 3 concentration to a value close to that of the control group. There was an elevation in neurotrophic factor protein level, along with augmented activity of pAkt and increased citrate synthase activity in the hippocampus after vitamin D 3 administration in long-term DEXA-treated rats. Our findings demonstrate that vitamin D 3 supplementation plays a protective role in the hippocampus and partially mitigates the deleterious effects of long-term DEXA administration. The association between serum 25(OH)D 3 concentration and BDNF level in the hippocampus indicates the importance of applying vitamin D 3 supplementation to prevent and treat pathological conditions.