TY  - JOUR
T1  - Gender-Dependent Cholinergic System Alterations in a Phenylketonuria Model
TT  - Fenilketonüri Modelinde Cinsiyete Bağlı Kolinerjik Sistem Değişiklikleri
AU  - Çiçek, Çiğdem
AU  - Gök, Müslüm
AU  - Bodur, Ebru
PY  - 2024
DA  - September
Y2  - 2024
JF  - Yüksek İhtisas Üniversitesi Sağlık Bilimleri Dergisi
JO  - YIU Saglik Bil Derg
PB  - Yüksek İhtisas Üniversitesi
WT  - DergiPark
SN  - 2717-8439
SP  - 60
EP  - 65
VL  - 5
IS  - 2
LA  - en
AB  - IntroductionPhenylketonuria (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 MethodsIn 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.ResultsHippocampal 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).ConclusionThese 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.
KW  - Phenylketonuria
KW  - Cholinergic system
KW  - Enzyme activity
KW  - Hippocampal tissue
KW  - Gender differences
N2  - GirişFenilketonüri (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 MetotÇalışmada, 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.BulgularPKU 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).SonuçBu 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.
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https://doi.org/10.47572/muskutd.1388547
UR  - https://dergipark.org.tr/tr/pub/yuksekihtisas/issue//1541266
L1  - https://dergipark.org.tr/tr/download/article-file/4180802
ER  -