PUBLICATION

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

Authors
Uthaiah, C.A., Devaru, N.C., Shivakumar, N.H., R, R., Madhunapantula, S.V.
ID
ZDB-PUB-221115-22
Date
2022
Source
Antioxidants (Basel, Switzerland)   11(11): (Journal)
Registered Authors
Keywords
Nrf2, cognition impairment, diabetes, oxidative stress, sulforaphane, vitamin D, zebrafish
MeSH Terms
none
PubMed
36358486 Full text @ Antioxidants (Basel)
Abstract
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.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping