Effects of vitamin D (VD3) supplementation on the brain mitochondrial function of male rats, in the 6-OHDA-induced model of Parkinson's disease

Mitochondria dysfunction is an important factor involved in PD pathogenesis. We reported neuroprotective actions of vitamin D (VD3) on a PD model, and now we investigated the VD3 effects on the brain mitochondrial function. We focused on oxygen consumption, respiratory control ratio (RCR), ADP/O ratio, mitochondria swelling, H2O2 production, and SOD activity. Additionally, immunohistoche mistry assays for the dopamine system markers (TH and DAT) and mitochondrial markers (VDAC1 and Hsp60) were also carried out in the striata. Young adult male Wistar rats (250 g, 2.5 months age) were anesthetized and subjected to stereotaxic surgery and injection of saline (SO group) or 6-OHDA, into the right striatum. Brain mitochondria were isolated from the groups: sham-operated (SO), 6-OHDA, 6-OHDA pretreated with VD3 for 7, days before the 6-OHDA lesion (6-OHDA+VD3, pre-) or treated with VD3 for 14 days, after the 6-OHDA lesion (6-OHDA+VD3, post-). VD3 prevented decreases in oxygen consumption, RCR, and ADP/O ratio observed after 6-OHDA injury. Noteworthy, a very low (oxygen consumption and RCR) or no improvement (ADP/O) were observed in the 6-OHDA+VD3 post-group. VD3 also prevented the increased mitochondria swelling and H2O2 production and a decrease in SOD activity, respectively, in the 6-OHDA injured mitochondria. Also, VD3 supplementation protected the hemiparkinsonian brain from decreases in TH and DAT expressions and decreased the upregulation of mitochondrial markers, as VDAC 1 and Hsp60. In conclusion, VD3 showed neuroprotective actions on brain mitochondria injured by 6-OHDA and should stimulate translational studies focusing on its use as a therapeutic strategy for the treatment of neurodegenerative diseases as PD.

Automated summary

Vitamin D3 (VD3) has neuroprotective effects on a PD model and can prevent the impairment of brain mitochondrial function caused by 6-OHDA. VD3 supplementation also protects the PD brain from damage to the dopamine system and mitochondrial markers.