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The Protective Effects of Policosanol on Learning and Memory Impairments in a Male Rat Model of Alzheimer’s Disease

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Abstract

Alzheimer’s disease (AD), the most common form of dementia, is characterized by a progressive decline in cognitive performance and memory formation. The present study was designed to investigate the effect of policosanol (PCO) on cognitive function, oxidative-antioxidative status, and amyloid-beta (Aβ) plaque formation in an AD rat model induced by intracerebroventricular (ICV) injection of Aβ1–40. Healthy adult male Wistar rats were randomly divided into seven groups: control, sham (5 μL, ICV injection of phosphate-buffered saline), AD model (5 μL, ICV injection of Aβ), acacia gum (50 mg/kg, 8 weeks, gavage), PCO (50 mg/kg, 8 weeks, gavage), AD + acacia gum (50 mg/kg, 8 weeks, gavage), and AD + PCO (50 mg/kg, 8 weeks, gavage). During the ninth and tenth weeks of the study, the cognitive function of the rats was assessed by commonly used behavioral paradigms. Subsequently, oxidative-antioxidative status was examined in the serum. Moreover, compact Aβ plaques were detected by Congo red staining. The results showed that injection of Aβ impaired recognition memory in the novel object recognition test, reduced the spatial cognitive ability in the Morris water maze, and alleviated retention and recall capability in the passive avoidance task. Additionally, injection of Aβ resulted in increased total oxidant status, decreased total antioxidant capacity, and enhanced Aβ plaque formation in the rats. Intriguingly, PCO treatment improved all the above-mentioned neuropathological changes in the Aβ-induced AD rats. The results suggest that PCO improves Aβ-induced cognitive decline, possibly through modulation of oxidative-antioxidative status and inhibition of Aβ plaque formation.

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Acknowledgements

The authors are grateful to the staff of the Neurophysiology Research Center, Hamadan University of Medical Sciences, for the role they had in doing this project.

Funding

The current study was funded (Grant No. IR.BASU.REC.1399.371) by the Faculty of Basic Sciences, Bu-Ali Sina University, Hamedan, Iran.

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Authors and Affiliations

  1. Department of Biology, Faculty of Basic Sciences, Bu-Ali Sina University, Hamedan, Iran

    Samaneh Safari, Naser Mirazi & Nesa Ahmadi

  2. Department of Neuroscience, School of Science and Advanced Technologies in Medicine, Hamadan University of Medical Sciences, Hamadan, Iran

    Samaneh Safari, Nesa Ahmadi, Masoumeh Asadbegi, Shahab Ghaderi & Alireza Komaki

  3. Department of Pathobiology, Faculty of Veterinary Science, Bu-Ali Sina University, Hamedan, Iran

    Alireza Nourian

  4. Student Research Committee, Asadabad School of Medical Sciences, Asadabad, Iran

    Masome Rashno

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  1. Samaneh Safari
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Contributions

Samaneh Safari: study concept and design, data acquisition, data analysis, interpretation, drafting of the manuscript, critical revision of the manuscript for important intellectual content, and statistical analysis.

Naser Mirazi: supervision, conceptualization, writing, review and editing, and data curation.

Nesa Ahmadi: preparation of the original draft and resources.

Masoumeh Asadbegi: data analysis and interpretation, formal analysis, and software validation.

Alireza Nourian: method validation.

Shahab Ghaderi: data analysis and revision of the manuscript.

Masome Rashno: data analysis and revision of the manuscript.

Alireza Komaki: study concept and design, critical revision of the manuscript for important intellectual content, and study supervision.

Corresponding author

Correspondence to Alireza Komaki.

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According to the Guidelines of the National Institutes of Health, the experiments were carried out on the principles of laboratory animal care (NIH Publication 80–23, 1996). The Local Ethical Committee approved all planned experimental procedures.

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Safari, S., Mirazi, N., Ahmadi, N. et al. The Protective Effects of Policosanol on Learning and Memory Impairments in a Male Rat Model of Alzheimer’s Disease. Mol Neurobiol 60, 2507–2519 (2023). https://doi.org/10.1007/s12035-023-03225-x

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