Antioxidants (Oct 2022)

Vitamin D Mitigates Hyperglycemia-Induced Cognition Decline in <i>Danio rerio</i> (Zebrafish) through the Activation of Antioxidant Mechanisms

  • Chinnappa A. Uthaiah,
  • Nandini C. Devaru,
  • Nandini H. Shivakumar,
  • Rajalakshmi R,
  • SubbaRao V. Madhunapantula

DOI
https://doi.org/10.3390/antiox11112114
Journal volume & issue
Vol. 11, no. 11
p. 2114

Abstract

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Hyperglycemia contributes to the development of cognition impairment and related disorders, induces oxidative stress in neuronal cells; thereby, impairs normal signaling mechanisms involved in cognition processes. Studies have shown a significant decrease in the vitamin D in individuals with hyperglycemia and cognition impairment. But whether supplementing vitamin D has any beneficiary impact on mitigating hyperglycemia-induced cognition impairment is unknown. We have first tested the impact of hyperglycemia on the induction of cognition deficiency in a zebrafish model. Next, the molecular mechanisms related to oxidative stress, which are deregulated in hyperglycemic zebrafish brains, have been explored. Subsequently, the impact of supplementing the water with vitamin D and a known activator of nuclear factor erythroid-2 related factor 2 (Nrf2) i.e., sulforaphane (SFN) on learning and memory functions were assessed. We showed a significant increase in the oxidative stress in the brain tissue of zebrafish residing in hyperglycemic water (111 mM glucose). Addition of vitamin D and SFN increased Nrf2, but differentially modulated its target genes (NQO1, SOD, GPx etc) activity in zebrafish and neuronal cell lines thereby improved the hyperglycemia-induced decline of cognition impairment. Mechanistically, vitamin D binds to the Keap1 protein; thereby, interfering with its binding to Nrf2, which leads to the activation of antioxidant mechanisms in the cells. In summary, reducing the oxidative stress through vitamin D treatment is a possible option for controlling the cognition impairment in diabetic population, but studies testing this possibility in clinical trials are currently needed.

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