Aquaporin 4 and 1 Expression Changes in the Brain of Pinealectomized Rats: Role of Melatonin

Year 2024, Volume: 12 Issue: 2, 702 - 722, 20.06.2024

Mehmet Demir , Feyza Başak

https://doi.org/10.33715/inonusaglik.1463177

Abstract

The brain's glymphatic system, a fluid exchange system, is associated with the aquaporin 4 (AQP4) water channels in astrocytes and aquaporin 1 (AQP1) in the ventricular choroid plexus. Circadian rhythms have also been reported to maintain fluid homeostasis in the brain. In this study, we aimed to determine the relationship between melatonin (pinealectomy and exogenous melatonin supplementation), which regulates circadian rhythm, and AQP4 and AQP1. The study, 50 male rats were divided into five groups (n=10). The groups were determined as Control, Sham Pinealectomy (Sham PX), Melatonin (MEL), Pinealectomy (PX), and PX+MEL. The MEL group received intraperitoneal injection of MEL (10 mg/kg/day) for 30 days, and the PX group received only PX surgery. We examined changes in AQP1 and AQP4 expression in brain tissue after PX surgery (MEL deprivation) and MEL injections. While there was no statistically significant difference in AQP1 and AQP4 levels between the control and Sham PX groups, a significant decrease was observed in the PX group (p<0.001). While an increase in AQP4 level was observed in the PX+MEL group (p<0.001), the AQP1 level did not change. This study demonstrated that MEL significantly contributed to the glymphatic system via AQP4 but not AQP1.

Keywords

Aquaporin 1, Aquaporin 4, Melatonin, Pinealectomy

PİNEALEKTOMİZE SIÇANLARIN BEYNİNDE AKUAPORİN 4 VE 1 EKSPRESYON DEĞİŞİKLİKLERİ: MELATONİNİN ROLÜ

Abstract

Beyinde bir sıvı değişim sistemi olan glenfatik sistem, astrositlerde akuaporin 4 (AQP4) ve ventriküler koroid pleksusta akuaporin 1 (AQP1) su kanalları ile ilişkilidir. Ayrıca beyinde sıvı homeostazının sürdürülmesinde sirkadiyen ritimlerin varlığı bildirilmiştir. Bu çalışmada sirkadiyen ritmi düzenleyen melatonin (pinealektomi ve eksojen melatonin takviyesi) ile AQP4 ve AQP1 arasındaki ilişkinin belirlenmesi amaçlanmıştır. Bu çalışmada 50 adet erkek sıçan beş gruba ayrıldı. Gruplar; Kontrol, Sham Pinealektomi (Sham PX), Melatonin (MEL), Pinealektomi (PX), PX+MEL olarak belirlendi. MEL grubuna 30 gün intraperitoneal MEL (10 mg/kg/gün) enjeksiyonu, PX grubuna ise sadece PX cerrahisi uygulandı. PX cerrahisi (MEL yoksunluğu) ve MEL enjeksiyonlarından sonra beyin dokusunda AQP1 ve AQP4 ifadelerindeki değişiklikler incelendi. AQP1 ve AQP4 seviyelerinde kontrol ve Sham PX grupları arasında istatistiksel olarak anlamlı bir fark yokken, PX grubunda anlamlı derecede bir azalma gözlenmiştir (p<0.001). PX+MEL grubunda AQP4 seviyesinde artış gözlenirken (p<0.001), AQP1 seviyesinin değişmediği tespit edilmiştir. Bu çalışma MEL’in AQP4 aracılığı ile glenfatik sisteme önemli katkı sağladığını ancak bu katkıyı AQP1 ile sağlayamadığını göstermiştir.

Keywords

Akuaporin 1, Akuaporin 4, Melatonin, Pinealektomi

Ethical Statement

Çalışma Karabük Üniversitesi Tıp Fakültesi Deney Hayvanları Etik Kurulu onayı ile gerçekleştirilmiştir (Tarih: 21/04/2022, Karar numarası: 2022/4/7, Kayıt numarası: E-55212866-050.99-125555). Tüm deneysel prosedürler, deney hayvanlarının kullanımına ilişkin Hayvan Etik Kurulu Yönergesine uygun olarak gerçekleştirilmiştir.

Supporting Institution

Bu proje Karabük Üniversitesi Bilimsel Araştırma Projeleri Yönetim Birimi tarafından desteklenmiştir (KBÜBAP-22-KP-144).

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