Bipolar mani modeli oluşturulmuş ratlarda olanzapinin prefrontal korteks ve hipokampusta IGF-1 ve IGF-1R üzerine etkisi
The effect of olanzapine on IGF-1 and IGF-1R in the prefrontal cortex and hypocampus in rats with a model of bipolar mania
Yazar: ESER ÇAKMAK
Danışman: PROF. DR. ÖZGÜR KORHAN TUNÇEL
Ondokuz Mayıs Üniversitesi / Lisansüstü Eğitim Enstitüsü / Tıbbi Biyokimya Ana Bilim Dalı
Derece: Doktora, 2023
Konu: Biyokimya = Biochemistry
Dizin: Bipolar bozukluk = Bipolar disorder ; Hipokampus = Hippocampus ; Maniler = Manis ; Olanzapine = Olanzapine ; Prefrontal korteks = Prefrontal cortex ; Reseptörler-insülin = Receptor-insulin ; Sıçanlar = Rats ; İnsülin benzeri büyüme faktörü I = Insulin like growth factor I

Özet:
Çalışmanın amacı, bipolar bozukluğun ortaya çıkışı ve olanzapin ile tedavisinde insülin benzeri büyüme faktörü 1 (IGF-1) ve reseptöründe (IGF-1R) meydana gelen değişiklikleri tespit etmektir.
48 yetişkin erkek albino wistar ratlardan kontrol grubuna (n=12) salin (0,5 ml), ketamin grubuna (n=12) ketamin (0,5 ml, 25 mg/kg), olanzapin grubuna (n=12) olanzapin (0,5 ml, 2 mg/kg), ketamin+olanzapin grubuna (n=12) ketamin (0,5 ml, 25 mg/kg) günde bir kez 14 gün boyunca intraperitoneal uygulanmıştır. Ketamin+olanzapin grubuna 8-14 günleri arasında ketamin uygulamasına ilaveten olanzapin (0,5 ml, 2 mg/kg) günde 1 kez uygulanmıştır. Prefrontal korteks ve hipokampusta hacim, IGF-1 ve IGF-1R gen ekspresyon ve protein düzeyi ölçümü yapılmıştır.
Prefrontal kortekste ketamin ile bipolar mani modeli oluşturulan grupta hacimde, IGF-1R gen ekspresyon ve protein düzeylerinde (immün boyama) azalma; olanzapin grubunda IGF-1 gen ekspresyon ve protein düzeylerinde (immun boyama) artış; ketamin+olanzapin grubunda IGF-1R gen ekspresyon, IGF-1 ve IGF-1R protein düzeylerinde (immün boyama) artış tespit ettik. Hipokampusta ketamin ile bipolar mani modeli oluşturulan grupta hacimde, IGF-1 gen ekspresyon ve protein düzeylerinde azalma; olanzapin grubunda hacimde ve IGF-1 protein düzeylerinde azalma, IGF-1R gen ekspresyon ve protein düzeylerinde (immun boyama) artış; ketamin+olanzapin grubunda hacimde, IGF-1 protein düzeyleri ve IGF-1R gen ekspresyon ve protein düzeylerinde azalma tespit ettik.
Bipolar bozukluğun altında yatan sebeplerden biri prefrontal korteks ve hipokampusta IGF-1 ve IGF-1R düzeyindeki değişiklikler olabilir. Tedavide kullanılan olanzapin, prefrontal kortekste IGF-1 ve IGF-1R düzeylerini arttırarak nöroprotektif bir etki, hipokampusta ise IGF-1 ve IGF-1R düzeylerinde azalmaya sebep olarak nörodejeneratif bir etki göstermektedir.

Abstract:
The aim of the study is to determine the changes in insulin-like growth factor 1 (IGF-1) and its receptor (IGF-1R) in the emergence of bipolar disorder and its treatment with olanzapine.
Of all 48 adult male albino wistar rats, the control group (n=12) saline (0.5 ml), ketamine group (n=12) ketamine (0.5 ml,25 mg/kg), olanzapine group (n=12) olanzapine (0.5 ml,2 mg/kg), ketamine+olanzapine group (n=12) ketamine (0.5 ml, 25 mg/kg) was administered intraperitoneally once a day for 14 days. In addition to ketamine administration, olanzapine (0.5 ml,2 mg/kg) was administered once a day to ketamine+olanzapine group between 8-14 days. Volume, IGF-1 and IGF-1R gene expression and protein levels were measured in prefrontal cortex and hippocampus. 
We detected that there was a decrease in volume of prefrontal cortex, IGF-1R gene expression and protein levels (immune staining) in the group in which bipolar mania model was created with ketamine; an increase in IGF-1 gene expression and protein levels (immune staining) in the olanzapine group; an increase in IGF-1R gene expression, IGF-1 and IGF-1R protein levels (immune staining) in the ketamine+olanzapine group in the prefrontal cortex. We detected that there was a decrease in volume of hippocampus, IGF-1 gene expression and protein levels in the group in which bipolar mania model was created with ketamine; a decrease in volume and IGF-1 protein levels, increase in IGF-1R gene expression and protein levels (immune staining) in the olanzapine group; a decrease in volume, IGF-1 protein levels and IGF-1R gene expression and protein levels in the ketamine+olanzapine group in the hippocampus.
We detected that there was a decrease in volume of prefrontal cortex, IGF-1R gene expression and protein levels (immune staining) in the group in which bipolar mania model was created with ketamine; an increase in IGF-1 gene expression and protein levels (immune staining) in the olanzapine group; an increase in IGF-1R gene expression, IGF-1 and IGF-1R protein levels (immune staining) in the ketamine+olanzapine group in the prefrontal cortex. We detected that there was a decrease in volume of hippocampus, IGF-1 gene expression and protein levels in the group in which bipolar mania model was created with ketamine; a decrease in volume and IGF-1 protein levels, increase in IGF-1R gene expression and protein levels (immune staining) in the olanzapine group; a decrease in volume, IGF-1 protein levels and IGF-1R gene expression and protein levels in the ketamine+olanzapine group in the hippocampus.