Vitamin K2 Ameliorates Diabetes-Associated Cognitive Decline by Reducing Oxidative Stress and Neuroinflammation.
Animals
Oxidative Stress
/ drug effects
Mice
Cognitive Dysfunction
/ drug therapy
Diabetes Mellitus, Experimental
/ drug therapy
Male
Neuroinflammatory Diseases
/ drug therapy
Hippocampus
/ drug effects
Acetylcholinesterase
/ metabolism
NF-E2-Related Factor 2
/ metabolism
Sirtuin 1
/ metabolism
Maze Learning
/ drug effects
GPI-Linked Proteins
Antioxidant
Inflammation
Memory
Vitamin
Journal
Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology
ISSN: 1557-1904
Titre abrégé: J Neuroimmune Pharmacol
Pays: United States
ID NLM: 101256586
Informations de publication
Date de publication:
28 Oct 2024
28 Oct 2024
Historique:
received:
02
08
2024
accepted:
15
10
2024
medline:
28
10
2024
pubmed:
28
10
2024
entrez:
28
10
2024
Statut:
epublish
Résumé
Diabetes, a chronic metabolic disease, affects approximately 422 million people and leads to 1.5 million deaths every year, It is found that 45% of individuals with diabetes eventually develop cognitive impairment. Here we study effects of Vitamin K2 on diabetes-associated cognitive decline (DACD) and its underlying mechanism. Diabetes was induced in adult Swiss albino mice with high-fat diet and a low dose (35 mg/kg) of streptozotocin and measured by fasting glucose and HbA1c levels. After one week of development of diabetes, one group of animals received Vitamin K2 (100 µg/kg) via oral gavage for 21 days. Then different behavioural studies, including the elevated plus maze, Morris water maze, passive avoidance test and novel object recognition test were performed followed by biochemical tests including AchE, different oxidative stress parameters (SOD, GSH, MDA, catalase, SIRT1, NRF2), inflammatory markers (TNFα, IL1β, MCP1, NFκB), apoptosis marker (Caspase 3). Hippocampal neuronal density was measured using histopathology. Vitamin K2 treatment in diabetic animals led to reduced fasting glucose and HbA1c, It could partially reverse DACD as shown by behavioural studies. Vitamin K2 adminstration reduced corticohippocampal AchE level and neuroinflammation (TNFα, IL1β, MCP1, NFκB, SIRT1). It reduced oxidative stress by increasing antioxidant enzymes (SOD, GSH, catalase), transcription factor NRF2 while reducing caspase 3. This eventually increased CA1 and CA3 neuronal density in diabetic animals. Vitamin K2 partially reverses DACD by increasing ACh while reducing the oxidative stress via Nrf2/ARE pathway and neuroinflammation, thus protecting the hippocampal neurons from diabetes associated damage.
Identifiants
pubmed: 39466454
doi: 10.1007/s11481-024-10156-4
pii: 10.1007/s11481-024-10156-4
doi:
Substances chimiques
Acetylcholinesterase
EC 3.1.1.7
NF-E2-Related Factor 2
0
Nfe2l2 protein, mouse
0
Ache protein, mouse
EC 3.1.1.7
Sirtuin 1
EC 3.5.1.-
GPI-Linked Proteins
0
Types de publication
Journal Article
Letter
Langues
eng
Sous-ensembles de citation
IM
Pagination
56Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
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