Hippocampal mitochondrial Ca in experimentally induced Alzheimer's disease, link to calpains and impact of vitamin D3 supplementation.

Unlabelled: Vitamin D impact on hippocampal mitochondrial Ca and calpains was not previously investigated in Alzheimer's disease (AD). The current work aimed to assess the alteration in hippocampal mitochondrial Ca, ATP & ADP and hippocampal calpains' level in (AlCl)-induced AD model, and the effect of 2 regimens of vitamin D supplementation on these alterations.

Methods: Forty male Wistar rats were randomized into 4 groups; control, AD (AlCl100 mg/kg, p.o. daily for 42 days), AD and vitamin D co-treated group (AlCl as in AD group with vitamin D 400 IU/kg/day, for 42 days) and AD, followed by vitamin D group (AlCl was given as in AD group for 42 days, then vitamin D for two weeks). AD was assessed by hippocampal levels of Aβ, p-tau and spatial memory assessment in Morris water maze. Hippocampal mitochondrial Ca, ATP and ADP levels besides to calpain-1 & 2 and cytochrome C were assessed in addition to CA1 histological examination.

Results: AD animals showed impaired mitochondrial function as denoted by high Ca and decreased ATP and ADP and elevated calpain-1 & 2 and cytochrome C. Hippocampal CA1 region showed increased degenerated neurons and reduced thickness of its pyramidal layer. Vitamin D administration minimized the hippocampal mitochondrial impairement induced by AD and mitigated histological alterations even when supplemented post AD establishment.

Conclusion: Vitamin D administration to AD rats breaks the deleterious loop in the hippocampus that involves increased Ca, calpain activation, mitochondrial failure, neuronal degeneration and AD disease progression.