Gender-Dependent Cholinergic System Alterations in a Phenylketonuria Model

Year 2024, Volume: 5 Issue: 2, 60 - 65, 20.09.2024

Çiğdem Çiçek , Müslüm Gök , Ebru Bodur

Abstract

Introduction
Phenylketonuria (PKU) is a rare inherited metabolic disorder characterized by a deficiency of the enzyme phenylalanine hydroxylase. The absence of this enzyme leads to elevated levels of phenylalanine in the blood, causing accumulation in the brain and resulting in permanent brain damage. To investigate the neurological effects of PKU, an experimental PKU model was developed, and cholinergic parameters were analyzed in brain tissue and serum from both female and male rats. In this study, serum BChE, AChE, and total ChE enzyme activities were examined, while AChE enzyme activity was specifically analyzed in hippocampal tissue.
Materials and Methods
In this study, brain tissue and serum samples were collected from female and male rats with an induced phenylketonuria model for analysis. BChE, AChE, and total ChE enzyme activities were measured in serum samples, while AChE enzyme activity was examined in hippocampal tissue. In the female PKU group, AChE activity was found to be 34.67±2.94 µU/mg, compared to 24.28±3.78 µU/mg in the female control group. Similarly, in the male PKU group, hippocampal AChE enzyme activity was 30.32±3.85 µU/mg, while it was 4.21±0.72 µU/mg in the male control group.
Results
Hippocampal AChE enzyme activity was significantly increased in both PKU groups compared to the control groups (Male ***p=0.0001; female *p=0.046). Serum analysis revealed decreased total serum cholinergic activity in both the female and male PKU groups compared with the control groups (**p≤0.002 and ***p≤0.0003, respectively). These results were consistent with findings from total serum cholinergic activity analysis. Additionally, the AChE enzyme activity in both the female and male PKU groups was decreased compared to their respective control groups (***p≤0.002 and ***p≤0.0006, respectively). It was also found that BChE enzyme activity in the serum of male rats in the PKU group was decreased compared to male rats in the control group (*p=0.038).
Conclusion
These findings indicate that the elements of the cholinergic system in the phenylketonuria model may vary according to gender. The observed changes in both brain tissue and serum provide new insights into the gender-dependent neurological effects of PKU.

Keywords

Phenylketonuria, Cholinergic system, Enzyme activity, Hippocampal tissue, Gender differences

Fenilketonüri Modelinde Cinsiyete Bağlı Kolinerjik Sistem Değişiklikleri

Abstract

Giriş
Fenilketonüri (PKU), fenilalanin hidroksilaz enziminin eksikliği ile karakterize nadir bir kalıtsal metabolik bozukluktur. Bu enzimin yokluğu, kandaki fenilalanin düzeyinin artmasına ve beyinde birikmesine neden olarak kalıcı beyin hasarına yol açar. PKU'nun nörolojik etkilerini incelemek amacıyla geliştirilen deneysel PKU modeli, hem dişi hem de erkek sıçanlarda kolinerjik parametrelerin beyin dokusu ve serumda analiz edilmesini sağlamıştır. Bu çalışmada serumda BChE, AChE ve toplam ChE enzim aktiviteleri incelenmiş, hipokampal dokuda ise AChE enzim aktivitesi değerlendirilmiştir.
Materyal ve Metot
Çalışmada, fenilketonüri modeli oluşturulan dişi ve erkek sıçanlardan beyin dokusu ve serum örnekleri alınarak analizler gerçekleştirilmiştir. Serum örneklerinde BChE, AChE ve toplam ChE enzim aktiviteleri ölçülürken, hipokampal dokuda yalnızca AChE enzim aktivitesi incelenmiştir. Dişi PKU grubunda AChE aktivitesi 34.67±2.94 µU/mg olarak bulunmuşken, dişi kontrol grubunda bu değer 24.28±3.78 µU/mg olarak ölçülmüştür. Benzer şekilde, erkek PKU grubunda hipokampal AChE enzim aktivitesi 30.32±3.85 µU/mg iken, erkek kontrol grubunda 4.21±0.72 µU/mg olarak tespit edilmiştir.
Bulgular
PKU gruplarında hipokampal AChE enzim aktivitesi, kontrol gruplarına kıyasla anlamlı derecede artış göstermiştir (Erkek ***p=0.0001; dişi *p=0.046). Serum analizlerinde ise dişi ve erkek PKU gruplarında toplam serum kolinerjik aktivitesinin kontrol gruplarına göre azaldığı belirlenmiştir (**p≤0.002 ve ***p≤0.0003, sırasıyla). Toplam serum kolinerjik aktivitesi bulguları, bu sonuçlarla uyumlu olarak değerlendirilmiştir. Dişi ve erkek PKU gruplarının AChE enzim aktivitesi, kontrol gruplarına göre azalmış (**p≤0.002 ve ***p≤0.0006, sırasıyla) olup, erkek sıçanlarda BChE enzim aktivitesinin de PKU grubunda kontrol grubuna göre azaldığı bulunmuştur (*p=0.038).
Sonuç
Bu bulgular, fenilketonüri modelinde kolinerjik sistemin unsurlarının cinsiyete göre farklılık gösterebileceğini göstermektedir. Hem beyin dokusunda hem de serumda gözlemlenen bu değişiklikler, PKU'nun cinsiyete bağlı nörolojik etkileri üzerine yeni bakış açıları sunmaktadır.

Keywords

Fenilketonüri, Kolinerjik sistem, Enzim aktivitesi, Hipokampal doku, Cinsiyet farklılıkları

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