Neuroprotective effect of ranolazine improves behavioral discrepancies in a rat model of scopolamine-induced dementia

Shereen M Samir; Hend M Hassan; Rasha Elmowafy; Eman Mohamed ElNashar; Mansour Abdullah Alghamdi; Mona Hmoud AlSheikh; Norah Saeed Al-Zahrani; Faten Mohammed Alasiri; Mona G Elhadidy

doi:10.3389/fnins.2023.1267675

Neuroprotective effect of ranolazine improves behavioral discrepancies in a rat model of scopolamine-induced dementia

Front Neurosci. 2024 Jan 12:17:1267675. doi: 10.3389/fnins.2023.1267675. eCollection 2023.

Authors

Affiliations

¹ Department of Medical Physiology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
² Department of Human Anatomy and Embryology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
³ Department of Medical Biochemistry and Molecular Biology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
⁴ Department of Anatomy, College of Medicine, King Khalid University, Abha, Saudi Arabia.
⁵ Genomics and Personalized Medicine Unit, College of Medicine, King Khalid University, Abha, Saudi Arabia.
⁶ Department of Physiology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia.
⁷ Department of Clinical Biochemistry, College of Medicine, King Khalid University, Abha, Saudi Arabia.
⁸ Pharmacist in King Fahad Armed Forces Hospital Khamis Mushait, Khamis Mushait, Saudi Arabia.
⁹ Department of Medical Physiology, Faculty of Medicine, Al-Baha University, Al-Baha, Saudi Arabia.

^# Contributed equally.

Abstract

Background: Ranolazine (Rn), an antianginal agent, acts in the central nervous system and has been used as a potential treatment agent for pain and epileptic disorders. Alzheimer's disease (AD) is one of the most prevalent neurodegenerative diseases and the leading factor in dementia in the elderly.

Aim: We examined the impact of Rn on scopolamine (Sco)-induced dementia in rats.

Methods: Thirty-two albino male rats were divided into four groups: control, Rn, Sco, and Rn + Sco.

Results: A significant decrease in the escape latency in the Morris water maze test after pre-treatment with Rn explained better learning and memory in rats. Additionally, Rn significantly upregulated the activities of the antioxidant enzymes in the treated group compared to the Sco group but substantially reduced acetylcholinesterase activity levels in the hippocampus. Moreover, Rn dramatically reduced interleukin-1 β (IL-1β) and IL-6 and upregulated the gene expression of brain-derived neurotrophic factor (BDNF). Furthermore, in the Sco group, the hippocampal tissue's immunohistochemical reaction of Tau and glial factor activating protein (GFAP) was significantly increased in addition to the upregulation of the Caspase-3 gene expression, which was markedly improved by pre-treatment with Rn. The majority of pyramidal neurons had large vesicular nuclei with prominent nucleoli and appeared to be more or less normal, reflecting the all-beneficial effects of Rn when the hippocampal tissue was examined under a microscope.

Conclusion: Our findings indicated that Rn, through its antioxidative, anti-inflammatory, and anti-apoptotic effects, as well as the control of the expression of GFAP, BDNF, and Tau proteins, has a novel neuroprotective impact against scopolamine-induced dementia in rats.

Keywords: GFAP; apoptosis; dementia; ranolazine; rats; scopolamine; tau.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. Deanship of Scientific Research at King Khalid University for funding this work through large group Research Project under grant number RGP2/291/44.