Deneysel Alzheimer Benzeri Demans Modelinde Trpc4/5 İnhibitörü M084'ün Etkilerinin Araştırılması

Abstract

Amaç: Bu çalışmadaki amacımız skopolamin ile oluşturduğumuz deneysel Alzheimer benzeri demans modelinde N-butil-[lH]-benzimidazol-2-amin (M084)’in bilişsel fonksiyonlar üzerine etkilerini araştırmaktır.
Araçlar ve Yöntem: Çalışmamızda erkek BALB/c fareler beş gruba (n:8) ayrıldı. Kontrol grubu; 14 gün boyunca günde 1 ml 0.9% salin çözeltisi intraperitoneal (i.p.) olarak uygulandı. Skopolamin grubu: İlk 7 gün günde 1 ml 0.9% salin çözeltisi, ardından 8-14. günler arasında günde 3 mg/kg skopolamini.p. olarak uygulandı. Skopolamin + M084 grubu; İlk 7 gün günde 1 ml 0.9% salin çözeltisi uygulanan farelere 8-14. günler arasında günde 3 mg/kg skopolamini.p. + 10-14 günler arası günde 20 mg/kg M084 günde tek doz i.p. olarak uygulandı. M084 grubu; farelere 0-14. günler arası günde 20 mg/kg M084 günde tek doz i.p. uygulandı. Donepezil grubu: Pozitif kontrol grubu olarak farelere 0-14. günler arası günde 5 mg/kg donepezili.p + 8-14 günler arasında günde 3 mg/kg skopolamini.p. uygulandı. Çalışmanın 14 ve 15. günlerinde pasif sakınma, yeni obje tanıma ve modifiye yükseltilmiş artı labirenti testi uygulamaları yapıldı.
Bulgular: Pasif sakınma testinde karanlık odaya geçiş süreleri skopolamin grubunda kontrol grubuna kıyasla daha kısaydı. Modifiye Yükseltilmiş Artı Labirenti Testinde 2. gün kapalı kollardan birine geçiş süreleri skopolamin grubunda kontrol ve donezepil grubuna göre daha fazla bulundu. Yeni obje tanıma testinde diskriminasyon indeks değerleri kontrol, skopolamin + M084, donezepil ve diğer gruplardaki değerler skopolamin grubuna göre daha fazla bulundu.
Sonuç: Sonuç olarak Alzheimer benzeri demans modelinde M084 görsel bellek üzerine olumlu sonuçlar vermiş, fakat diğer bellek türleri üzerine etkisiz bulunmuştur.

Keywords

• M084
• Alzheimer
• skopolamin
• bellek fonksiyonları

Investigation of The Effects of Trpc4/5 Inhibitor M084 in Experimental Alzheimer’s-LikeDementia Model

Abstract

Purpose: This study aimed to research the effects of N-butyl-1H]-benzimidazole-2-amine (M084) on cognitive functions in an experimental Alzheimer-like dementia model.
Materials and Methods: In our study, male rats were divided into five groups (n:8). The control (C) had 1 ml 0.9% saline solution administered intraperitoneally (i.p.) for 14 days. Scopolamine (S) was administered intraperitoneally with 1 ml 0.9% saline solution for the first 7 days, followed by 3 mg/kg scopolamine on days 8-14.Scopolamine+M084 (SM) was administered i.p. dissolved in 1 ml 0.9% saline solution for the first 7 days, followed by 3 mg/kg scopolamine on days 8-14 and 20 mg/kg M084 on days 10-14. M084 (M) was administered i.p. 20 mg/kg M084 in a single daily dose from days 0-14. Positive control (D) had 5 mg/kg donepezil administrations on days 0-14 and 3 mg/kg scopolamine on days 8-14.
On days 14 and 15 of the study, passive avoidance, novel object recognition, and modified elevated plus maze tests were performed.
Results: In the passive avoidance test, transfer latencies were significantly lower in group S compared to group C. In the modified elevated plus maze test, the passing time to either closed arms on the 2nd-day test was significantly higher in group S compared to groups C and D. In the novel object recognition test, the values for groups C, SM, D, and other groups were significantly higher compared to group S.
Conclusion: In conclusion, in an Alzheimer-like dementia model, M084 provided positive results for visual memory; however, it was ineffective for other memory types. 

Keywords

• M084
• Alzheimer
• scopolamine
• memory functions

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