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

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

JOURNAL=Frontiers in Neuroscience

VOLUME=Volume 17 - 2023

YEAR=2024

URL=https://www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2023.1267675

DOI=10.3389/fnins.2023.1267675

ISSN=1662-453X

ABSTRACT=Background: Ranolazine (Rn), an antianginal agent, acts in the central nervous system and has been a potential treatment of 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 group; control, Rn, Sco, and Rn+ Sco. Results:A significant decrease in the escape latency in the Morris Water Maze test after pretreatment 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 Sco group, while substantially reducing acetylcholinesterase activity levels in the hippocampus. Also, Rn dramatically reduced interleukin-1 β (IL-1β), IL-6 and upregulated the gene expression for brainderived neurotrophic factor (BDNF). Furthermore, in Sco group, the hippocampal tissue's immunohistochemical reaction of Tau and glial factor activating protein (GFAP) was significantly increased, in addition to upregulation of the Caspase-3 gene expression, which was markedly improved by pretreatment 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 hippocampal tissue was examined under a microscope. Conclusion: Our findings indicated that Rn, through its antioxidative, anti-inflammatory, and anti-apoptotic activities as well as control of the expression of GFAP, BDNF, and Tau proteins, has a novel neuroprotective impact against scopolamine-induced dementia in rats.