Neurochemical Effects of the Adipokinetic Hormone/Red Pigment Concentrating Hormone Family of Peptides in MK-801-Induced Schizophrenia Rat Model

Abstract

Objective: Adipokinetic hormone (AKH) plays a role in sugar and lipid metabolism in insects. Previous studies of AKH showed memory improvements in a schizophrenia rat model that displayed memory impairment and reduced depression in a rat olfactory bulbectomy model. In this study, we investigated the effects of the adipokinetic hormone/red pigment-concentrating hormone (AKH/RPCH) family of peptides on brain neurotransmitter levels and brain neurochemistry in a schizophrenia rat model. Materials and Methods: We administered AKH/RPCH peptides for 4 days sub-chronically, both in naive rats and also in the MK-801-induced schizophrenia rat model. Liquid chromatography-mass spectrometry apparatus was used for targeted and untargeted analysis of rat neurochemistry. Results: Increased brain glutamate levels characteristic of MK-801 peptide-treated rats were significantly reduced by AKH. Furthermore, AKH also increased brain dopamine levels in both naive and MK-801 rats. Metabolomic studies have shown that AKH affects lipid and glutamate metabolism, while hypertrehalosaemic hormone plays a role in sugar metabolism and inflammation. Conclusion: According to our results, AKH might affect dopaminergic and glutamatergic systems and reverse the effects of MK-801, possibly affecting NMDA receptors.

Keywords

• Adipokinetic hormone
• neurochemistry
• neurotransmitters
• schizophrenia

Adipokinetik Hormon/Kırmızı Pigment Konsantre Hormon Peptid Ailesinin MK-801'in İndüklediği Şizofreni Sıçan Modelinde Nörokimyasal Etkileri

Öz

Amaç: Adipokinetik hormon (AKH) böceklerde şeker ve lipid metabolizmasında rol oynar. Önceki çalışmalarda AKH sıçan şizofeni modelinde belleği ve sıçan olfaktör bulbektomi modelinde depresyonu düzelttiği gösterilmiştir. Bu çalışmada, adipokinetik hormon/kırmızı pigment konsantre edici hormon (AKH/RPCH) ailesi peptidlerinin sıçan şizofreni modelinde beyin nörotransmitter seviyesi ve beyin nörokimyası üzerine etkisi araştırılmıştır. Materyal ve Metot: Peptidleri hem naif sıçanlarda hem de MK-801 ile indüklenmiş sıçan şizofreni modelinde 4 gün boyunca subkronik olarak uyguladık. Likid kromatografi-kütle spektrometri cihazı nörokimyanın hedeflenmiş ve hedeflenmemiş analizi için kullanıldı. Bulgular: AKH anlamlı olarak MK-801 uygulanmış sıçanlarda artmış beyin glutamat seviyesini düşürmüştür. AKH ayrıca hem naif sıçanlarda hem MK-801 uygulanmış sıçanlarda beyin dopamin seviyesini artırdı. Metabolomik çalışmalar adipokinetik hormonun lipid ve glutamat metabolizmasını etkilediğini, hipertrehalosemik hormonun ise şeker metabolizması ve enflamasyonda rol oynadığını gösterdi. Sonuç: Sonuçlarımıza göre AKH dopaminerjik ve glutamaterjik sistemi etkileyebilir ve MK-801’in etkilerini muhtemelen NMDA reseptörleri üzerinden tersine çeviriyor olabilir.

Anahtar Kelimeler

• Adipokinetik hormon
• nörokimya
• nörotransmitter
• şizofreni

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