Jul 1, 2020

Evaluation of the neuroprotective effect of donepezil in type 2 diabetic rats

Fundamental & Clinical Pharmacology
Adel A GomaaMariam A Nicola

Abstract

Recent studies raise the possibility that donepezil can delay the progression of Alzheimer's disease (AD). This research evaluated the efficacy of donepezil in an animal model with brain insulin resistance and AD-like alterations. Rats were fed with high-fat/high-fructose (HF/Hfr) diet during the study period (17 weeks) and received one injection of streptozotocin (STZ) (25mg/kg) after 8 weeks of starting the study. Diabetic (T2D) rats were treated with donepezil (4 mg/kg; p.o.) or vehicle for 8 weeks after STZ injection. The influence of donepezil on AD-related behavioral, biochemical and neuropathological changes were investigated in T2D rats. Treatment of diabetic rats with donepezil led to a significant decrease in both amyloid-β deposition and the raised hippocampal activity of cholinesterase (ChE). It significantly increased the suppressed glutamate receptor expression (AMPA GluR1 subunit and NMDA receptor subunits NR1, NR2A, NR2B). It also improved cognitive dysfunction in the passive avoidance and the Morris water maze tests. However, donepezil treatment did not significantly decrease the elevated levels of P-tau, caspase-3, GSK-3β, MDA, TNF-α and IL-1β in the hippocampus of diabetic rats. Also, it did not restore the s...Continue Reading

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Mentioned in this Paper

GRIN2A protein, human
glycogen synthase kinase 3 beta
CASP3
Signal Transduction Alteration
Caspase-3
Diabetes Mellitus, Non-Insulin-Dependent
Diabetes
GRIN2B protein, human
Insulin
Memory Impairment

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