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

• Published in: Neurological research (New York) Vol. 45; no. 6; pp. 544 - 553
• Main Authors: Topcu, Atilla, Saral, Sinan, Ozturk, Aykut, Saral, Ozlem, Kaya, Ali Koray
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 03-06-2023
• Subjects: Acetylcholine - metabolism; Acetylcholine - pharmacology; Acetylcholinesterase - metabolism; Animals; Brain-Derived Neurotrophic Factor - metabolism; Calcium Channel Blockers - metabolism; Calcium Channel Blockers - pharmacology; Cognitive Dysfunction - drug therapy; Cognitive Dysfunction - metabolism; Dementia; Hippocampus; Male; Maze Learning; nimodipine; Nimodipine - pharmacology; rat; Rats; Rats, Sprague-Dawley; Scopolamine; hippocampus; rat; scopolamine; nimodipine; Dementia
• ISSN: 0161-6412; 1743-1328
• DOI: 10.1080/01616412.2022.2164452

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