Vitamin D mitigates post-stroke depression by rescuing IL-6-mediated BDNF reduction

Post-stroke depression (PSD) is a common complication after stroke, while Vitamin D (VD) deficiency is common in stroke patients. This study aims to investigate the relationship between VD and PSD, as well as the underlying mechanisms.

390 patients with acute ischemic stroke (AIS) were assessed for PSD using Hamilton Depression Rating Scale at 1 month after stroke. PSD model rats were developed by middle cerebral artery occlusion with chronic unpredictable mild stress, and further classified into VD Normal (VDN), VD Deficiency (VDD), and VD-deficient rats receiving VD supplementation (VDS) groups. Depression-like behaviors were evaluated using sucrose preference test (SPT) and forced swim test (FST).

PSD patients had significantly lower VD levels compared with patients without depression. The effect of VD deficiency on PSD was mediated by IL-6 and BDNF (chain mediated effect = 0.004, 95%CI = 0.001 - 0.011, P = 0.032). VDD rats showed lower sucrose preference and higher immobility time compared with rats in VDN and VDS groups (P < 0.05). Consistently, increased IL-6 and decreased BDNF was detected in the hippocampus of VDD rats, while VDS mitigated PSD phenotype, as well as reducing IL-6 levels and increasing BDNF levels.

VD deficiency increases the risk of PSD, which is significantly associated with the upregulation of IL-6 and the subsequent downregulation of BDNF in both AIS patients and PSD model rats. Early VD supplementation mitigates PSD symptoms in rats, as well as suppressing IL-6 and enhancing BDNF. Our study demonstrated that VD supplementation is a potential effective approach for PSD intervention.