The effect of the calcium channel blocker nimodipine on hippocampal BDNF/Ach levels in rats with experimental cognitive impairment

ABSTRACT

Objective

Alzheimer’s disease (AD) occurs in approximately 10% to 30% of individuals aged 65 or older worldwide. Novel therapeutic agents therefore need to be discovered in addition to traditional medications. Nimodipine appears to possess the potential to reverse cognitive impairment-induced dysfunction in learning and memory through its regulatory effect on the brain-derived neurotrophic factor (BDNF), acetylcholine (Ach), and acetylcholinesterase (AChE) pathway in the hippocampus and prefrontal cortex.

Methods

Twenty-four male Sprague Dawley rats weighing 380 ± 10 g were used for behavioral and biochemical analyses. These were randomly and equally assigned into one of three groups. Group 1 received saline solution alone via the intraperitoneal (i.p) route, and Group 2 received 1 mg/kg/day i.p. scopolamine once a day for three weeks for induction of learning and memory impairments. In Group 3, 10 mg/kg/day nimodipine was prepared in tap water and administered orally every day for three weeks, followed after 30 min by 1 mg/kg/day scopolamine i.p. Behavior was evaluated using the Morris Water Maze test. BDNF, ACh, and AChE levels were determined using the ELISA test in line with the manufacturer’s instructions.

Results

Nimodipine treatment significantly increased the time spent in the target quadrant and the number of entries into the target quadrant compared to the scopolamine group alone. Additionally, BDNF and ACh levels in the hippocampus and prefrontal cortex decreased following 20-day scopolamine administration, while AChE activation increased.

Conclusion

Nimodipine exhibited potentially beneficial effects by ameliorating cognitive decline following scopolamine administration in the hippocampus and prefrontal cortex.

KEYWORDS:

• Dementia
• hippocampus
• nimodipine
• scopolamine
• rat

Highlights

• Alzheimer’s disease (AD) occurs in approximately 10% to 30% of individuals aged 65 or older worldwide.

• An experimental model of cognitive function impairment induced by scopolamine, objectively confirmed in much previous research, is frequently employed in studies on the subject

• Nimodipine once again exhibited potentially beneficial effects by ameliorating cognitive decline following scopolamine administration by acting on the hippocampus and prefrontal cortex.

Acknowledgments

The authors wish to thank Dr. Aysegul Sumer for her assistance with the biochemical analysis.

Disclosure statement

No authors have any conflict of interest to declare.

Authors’ contributions

AT and SS conceived the research. AT, SS, AO and AKK conducted the experiments. OS and AS contributed new reagents or analytical tools. SS and OS analyzed the data. AT wrote the manuscript. All authors read and approved the manuscript.

Additional information

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.