Evaluation of the effects of donepezil, memantine and α-lipoic acid combined administration in amnesia rats on impaired cognitive functions in terms of behavioural, apoptotic, cholinergic and glutamatergic systems

Year 2021, Volume: 11 Issue: 4, 733 - 741, 26.10.2021

Aslı Aykaç , Dilek Özbeyli , Gizem Pekol Ahmet Özer Şehirli

https://doi.org/10.33808/clinexphealthsci.856459

Cited By: 2

Abstract

Objective: The aim of the study was to evaluate the possible protective effects of alpha-lipoic acid (α-LA), donepezil and memantine combined therapy in the scopolamine-induced amnesia rat model.
Objective: The aim of the study was to evaluate the possible protective effect of donepezil, memantine and alpha-lipoic acid (α-LA) combined therapy in the scopolamine-induced amnesia rat model.
Methods: In this study, the effect of combined therapy used in the treatment of scopolamine-induced amnesia on behavioural parameters was evaluated using Y-maze and new object recognition (NOR) test. In addition, muscarinic acetylcholine receptor subtype M1, N-methyl-D-aspartate receptor NR2B subunit, brain-derived neurotrophic factor (BDNF) and mitochondrial apoptosis-related proteins [B-cell lymphoma-2 (Bcl-2) / Bcl-2 associated X (Bax) ratio, caspase (casp) -3, and -9] expression levels were evaluated using the western blot method in the frontal cortex and hippocampus regions.
Results: The main findings of this study demonstrated that in scopolamine-induced amnesia rats, cognitive dysfunction determined by both the Y-maze and the NOR test were reversed with the combined treatment of memantine, donepezil and α-LA. According to immunoblotting results in both brain regions, scopolamine-induced decreased M1, BDNF, Bcl-2 / Bax ratio and increased NR2B, casp-3 and -9 expression levels were found to be reversed to almost control values with combined treatment.
Conclusion: Consistent with the literature, our study results suggest that the positive contribution of α-LA to the combined treatment of donepezil and memantine, which is used in the routine treatment of neurodegenerative diseases, may be a treatment option in the future.
Results: The main findings of this study demonstrated that in scopolamine-induced amnesia rats, cognitive dysfunction determined by both the Y-maze and the NORT test were reversed with the combined treatment of memantine, donepezil and α-LA. In addition, decreased BDNF, M1, bcl-2/bax ratio and increased NR2B, caspase-3 and caspase-9 expression levels due to scopolamine in both regions were improved with α-LA, donepezil and memantine combined therapy.
Conclusion: The results of our study and other study results in the literature suggest that α-LA may be a future treatment option due to its positive contribution to the effects of other drugs used in the routine treatment of neurodegenerative diseases.

Keywords

alpha-lipoic acid, amnesia, apoptosis, scopolamine, Y-maze

Supporting Institution

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Project Number

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Thanks

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