Examination of Cognitive Functions and Hippocampal Synaptophysin Levels in an Experimental Schizophrenia Model

Şizofreni pozitif, negatif ve bilişsel belirtiler ile seyreden kronik bir beyin hastalığıdır. Bilişsel belirtiler hastalığın prodromal döneminden itibaren gözlenebilmektedir. Bu çalışmanın amacı irkilme refleksininin ön uyaran aracılı inhibisyonu (ÖUAİ) ile oluşturulan deneysel şizofreni modelinde sıçanların bilişsel fonksiyonlarını ve hipokampal presinaptik proteinlerden sinaptofizin düzeylerini araştırmaktır. Çalışmada 30 adet erkek Wistar türü sıçanlar bazal ÖUAİ ölçümüne tabi tutulmuş ve bu değerlere göre düşükten yükseğe sıralanmıştır. İlk 10 sıçan “düşük” ve son 10 sıçan “yüksek” inhibisyonlu grup olarak ayrıldıktan sonra 5 gün boyunca Morris Su Tankı (MST) testine tabi tutulmuştur. Testin bitiminde sıçanlar sakrifiye edilerek hipokampus bölgeleri eksize edilmiş ve hipokampal presinaptik proteinlerden sinaptofizin Western Blot yöntemiyle analiz edilmiştir. Sonuçlara göre her iki grubun öğrenme düzeyleri arasında fark bulunmaz iken ve hafıza fonksiyonlarının platform alanından geçme sıklığı (p<0,05) ve platform alanında geçirilen süre parametreleri (p<0,05) düşük ÖUAİ gruptaki sıçanlarda anlamlı olarak daha düşük bulunmuştur. Sinaptofizin düzeyleri de benzer şekilde düşük ÖUAİ grubundaki sıçanlarda anlamlı olarak (p<0,01) düşük tespit edilmiştir. Çalışmamızın sonuçları yüksek ÖUAİ değerine sahip sıçanlarla kıyaslandığında ÖUAİ değerleri düşük olan sıçanların bazı bilişsel fonksiyonlarının ve hipokampal presinaptik proteinlerden sinaptofizin düzeylerinin anlamlı olarak daha düşük olduğunu göstermektedir. Bu sonuçlar aynı zamanda uzun zamandır şizofreni çalışmalarında güvenilir bir yöntem olarak kullanılan ÖUAİ testinin insan ve hayvan çalışmalarındaki benzer sonuçlarına vurgu yaparak şizofreni araştırmalarındaki önemini desteklemiştir.Schizophrenia is a chronic brain disease and is clinically characterized by positive, negative and cognitive symptoms. Cognitive symptoms can be observed starting from the prodromal period of the disease. The aim of this study is to investigate the cognitive functions of rats and hippocampal levels of the presynaptic protein synaptophysin in an experimental schizophrenia model created by prepulse-mediated inhibition (PPI) of the startle reflex. In the study, 30 male Wistar type rats were subjected to basal PPI measurements and were ranked from low to high according to these values. After the first 10 rats were divided into the "low" and the last 10 rats into the "high" inhibition group, they were subjected to the Morris Water Maze (MWM) test for 5 days. At the end of the test, the rats were sacrificed, hippocampus regions were excised, and the presynaptic synaptophysin protein was analyzed by Western Blot method. According to the results, while there was no difference between the learning levels of both groups, the frequency of memory functions frequency to cross the platform area (p <0.05) and time spent in the platform area (p <0.05) parameters were found to be significantly lower in rats in the low PPI group. Synaptophysin levels were similarly found to be significantly (p<0.01) lower in rats in the low PPI group. The results of our study show that some cognitive functions and presynaptic protein synaptophysin levels are significantly lower in rats with low PPI values compared to those with high PPI values. These results also supported the importance of the PPI test, which has been used as a reliable method in schizophrenia research for a long time, by emphasizing its comparable outcomes in human and animal studies of schizophrenia

Glycyl-glutamine, an endogenous beta-endorphin-derived peptide, inhibits morphine-induced conditioned place preference, tolerance, dependence, and withdrawal

Glycyl-glutamine (Gly-Gln; beta-endorphin(30-31)) is an endogenous dipeptide synthesized from beta-endorphin(1-31). Previous investigations have shown that Gly-Gln inhibits the cardiovascular and respiratory depression caused by morphine and beta-endorphin(1-31), but it does not interfere with opioid analgesia. In this study, we tested whether Gly-Gln administration would influence morphine-induced conditioned place preference, tolerance, dependence, or withdrawal. For place preference experiments, rats were conditioned with morphine sulfate (2.5 mg/kg i.p.) or saline on alternate days for 6 days and tested on day 7. Glycyl-glutamine (1-100 nmol i.c.v.) pretreatment inhibited acquisition of a conditioned place preference to morphine significantly. Glycyl-glutamine (100 nmol i.c.v.) also blocked expression of a pre-established morphine place preference, but it did not interfere with acquisition of a conditioned place preference to palatable food, and it did not produce place preference or aversion when given alone to morphine-naive animals. To induce antinociceptive tolerance, rats were treated with morphine (10 mg/kg i.p.) twice daily for 7 days, and morphine antinociception was evaluated with the tail-flick test. Glycylglutamine (100 nmol i.c.v.) pretreatment delayed the onset of morphine tolerance significantly and partially reversed pre-established tolerance. Morphine dependence and withdrawal were assessed by measuring naloxone-precipitated withdrawal symptoms. Glycyl-glutamine inhibited the development of morphine dependence when given to rats twice daily immediately before they received morphine (10 mg/kg i.p.) and suppressed withdrawal symptoms of rats with subcutaneously implanted morphine pellets when administered 5 min before withdrawal was induced with naloxone. Glycyl-glutamine thus attenuates morphine-induced conditioned place preference, tolerance, dependence, and withdrawal without compromising morphine analgesia.United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute on Drug Abuse (NIDA) - DA018029United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute on Drug Abuse (NIDA) European Commission - R41DA01802