Dapagliflozin Ameliorates Cognitive Impairment in Aluminum-Chloride-Induced Alzheimer‚Äôs Disease via Modulation of AMPK/mTOR, Oxidative Stress and Glucose Metabolism

Pharmaceuticals · 6 authors, 4 centres

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TL;DR

This preclinical study used a rat model of Alzheimer's disease (AD) induced by chronic aluminum chloride (AlCl3) administration.

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This preclinical study used a rat model of Alzheimer's disease (AD) induced by chronic aluminum chloride (AlCl3) administration.

STUDY TYPE

other

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neurology

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ORIGINAL PAPER

PMC10223357

Dapagliflozin Ameliorates Cognitive Impairment in Aluminum-Chloride-Induced Alzheimer‚Äôs Disease via Modulation of AMPK/mTOR, Oxidative Stress and Glucose Metabolism

Pharmaceuticals

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ABSTRACT

Abstract Alzheimer‚Äôs disease (AD) is a progressive neurological illness characterized by memory loss and cognitive deterioration. Dapagliflozin was suggested to attenuate the memory impairment associated with AD; however, its mechanisms were not fully elucidated. This study aims to examine the possible mechanisms of the neuroprotective effects of dapagliflozin against aluminum chloride (AlCl 3 )-induced AD. Rats were distributed into four groups: group 1 received saline, group 2 received AlCl 3 (70 mg/kg) daily for 9 weeks, and groups 3 and 4 were administered AlCl 3 (70 mg/kg) daily for 5 weeks. Dapagliflozin (1 mg/kg) and dapagliflozin (5 mg/kg) were then given daily with AlCl 3 for another 4 weeks. Two behavioral experiments were performed: the Morris Water Maze (MWM) and the Y-maze spontaneous alternation (Y-maze) task. Histopathological alterations in the brain, as well as changes in acetylcholinesterase (AChE) and amyloid Œ≤ (AŒ≤) peptide activities and oxidative stress (OS) markers, were all evaluated. A western blot analysis was used for the detection of phosphorylated 5‚Äô AMP-activated protein kinase (p-AMPK), phosphorylated mammalian target of Rapamycin (p-mTOR) and heme oxygenase-1 (HO-1). Tissue samples were collected for the isolation of glucose transporters (GLUTs) and glycolytic enzymes using PCR analysis, and brain glucose levels were also measured. The current data demonstrate that dapagliflozin represents a possible approach to combat AlCl 3 -induced AD in rats through inhibiting oxidative stress, enhancing glucose metabolism and activating AMPK signaling. Keywords: Alzheimer‚Äôs disease, dapagliflozin, AMPK pathway, oxidative stress, glucose metabolism

CITATION EXPORT

Waad A Samman, Salma M Selim, Hassan M El Fayoumi et al.. Dapagliflozin Ameliorates Cognitive Impairment in Aluminum-Chloride-Induced Alzheimer‚Äôs Disease via Modulation of AMPK/mTOR, Oxidative Stress and Glucose Metabolism. Pharmaceuticals. (2023). https://doi.org/10.3390/ph16050753

AUTHORS

6 · 4 CENTRES

Waad A Samman, Salma M Selim, Hassan M El Fayoumi, Norhan M El-Sayed, Eman T Mehanna, Reem M Hazem

1Department of Pharmacology and Toxicology, College of Pharmacy, Taibah University, Medina 30078, Saudi Arabia
2Department of Pharmacology and Toxicology, Faculty of Dentistry, Sinai University, Kantara, Ismailia 41636, Egypt
3Department of Pharmacology and Toxicology, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt
4Department of Biochemistry, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt