Investigation of the effects of TRPC4 / 5 inhibitor M084 in experimental alzheimer-like dementia model

Aim: Our aim in this study is to investigate the effects of N-butyl- [1H] -benzimidazole-2-amine (M084) on cognitive functions in an experimental alzheimer-like dementia model created with scopolamine. Materials and Methods: In our study, male mice were divided into six groups (n: 8). Control group; For 14 days, 1 ml of 0.9% saline solution was administered intraperitoneally (i.p.) per day. Scopolamine group: Subjects were administered 1 ml 0.9% saline solution daily for the first 7 days (i.p.) and 3 mg / kg scopolamine daily for 8-14 days (i.p.). M084 + Scopolamine group; Subjects received a single dose (i.p) of 20 mg / kg M084 per day between 0-14 days and 3 mg / kg scopolamine (i.p.) per day between 8-14 days. Scopolamine + M084 group; For the first 7 days, 1 ml of 0.9% saline solution (i.p.) was applied daily and 3 mg / kg scopolamine (i.p.) daily for 8-14 days, and 20 mg / kg M084 daily for 10-14 days as a single dose (i.p). M084 group; Subjects received a single dose (i.p) of 20 mg / kg M084 per day between 0-14 days. Donepezil group: As a positive control group, subjects received 5 mg / kg donepezil (i.p) daily between 0-14 days and 3 mg / kg scopolamine (i.p.) daily between 8-14 days. On the 14th and 15th days of the study, open area, passive avoidance, foreign object recognition and modified plus maze tests were performed. Neurotrophic factor (BDNF), TAU, Aβ-42, CREB values were analyzed in brain tissue samples. Results: In the open area test; The mean speed, distance and open area peripheral frequency values were significantly increased in the scopolamine group compared to the control group. In the passive area test; transition time was significantly lower in scopolamine group compared to the control group. In Modified Plus T Test; T2 duration was significantly higher in the scopolamine group compared to the control and donezepil group. In the new object recognition test; The values in the control group, scopolamine-M084 group, donezepil group and other groups were significantly higher than the scopolamine group. When the BDNF values were analyzed, the scopolamine group decreased significantly compared to the control group, while the scopolamine-M084 group increased compared to the control group but was not statistically significant. Tau and Abeta42 levels increased in scopolamine group compared to the control group but were not statistically significant. Creb level decreased in scopolamine group compared to control group, but it was not found statistically significant. Conclusion: As a result, in the Alzheimer's-like dementia model, M084 gave positive results on visual memory, but was found to be ineffective on other types of memory.