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

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 hypergl...

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Autores principales: Uthaiah, Chinnappa A., Devaru, Nandini C., Shivakumar, Nandini H., R, Rajalakshmi, Madhunapantula, SubbaRao V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9686813/
https://www.ncbi.nlm.nih.gov/pubmed/36358486
http://dx.doi.org/10.3390/antiox11112114
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author Uthaiah, Chinnappa A.
Devaru, Nandini C.
Shivakumar, Nandini H.
R, Rajalakshmi
Madhunapantula, SubbaRao V.
author_facet Uthaiah, Chinnappa A.
Devaru, Nandini C.
Shivakumar, Nandini H.
R, Rajalakshmi
Madhunapantula, SubbaRao V.
author_sort Uthaiah, Chinnappa A.
collection PubMed
description 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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spelling pubmed-96868132022-11-25 Vitamin D Mitigates Hyperglycemia-Induced Cognition Decline in Danio rerio (Zebrafish) through the Activation of Antioxidant Mechanisms Uthaiah, Chinnappa A. Devaru, Nandini C. Shivakumar, Nandini H. R, Rajalakshmi Madhunapantula, SubbaRao V. Antioxidants (Basel) Article 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. MDPI 2022-10-27 /pmc/articles/PMC9686813/ /pubmed/36358486 http://dx.doi.org/10.3390/antiox11112114 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Uthaiah, Chinnappa A.
Devaru, Nandini C.
Shivakumar, Nandini H.
R, Rajalakshmi
Madhunapantula, SubbaRao V.
Vitamin D Mitigates Hyperglycemia-Induced Cognition Decline in Danio rerio (Zebrafish) through the Activation of Antioxidant Mechanisms
title Vitamin D Mitigates Hyperglycemia-Induced Cognition Decline in Danio rerio (Zebrafish) through the Activation of Antioxidant Mechanisms
title_full Vitamin D Mitigates Hyperglycemia-Induced Cognition Decline in Danio rerio (Zebrafish) through the Activation of Antioxidant Mechanisms
title_fullStr Vitamin D Mitigates Hyperglycemia-Induced Cognition Decline in Danio rerio (Zebrafish) through the Activation of Antioxidant Mechanisms
title_full_unstemmed Vitamin D Mitigates Hyperglycemia-Induced Cognition Decline in Danio rerio (Zebrafish) through the Activation of Antioxidant Mechanisms
title_short Vitamin D Mitigates Hyperglycemia-Induced Cognition Decline in Danio rerio (Zebrafish) through the Activation of Antioxidant Mechanisms
title_sort vitamin d mitigates hyperglycemia-induced cognition decline in danio rerio (zebrafish) through the activation of antioxidant mechanisms
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9686813/
https://www.ncbi.nlm.nih.gov/pubmed/36358486
http://dx.doi.org/10.3390/antiox11112114
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