Role of Insulin in Synaptic Plasticity; Long Term Depression

Öz

Introduction: Insulin is a hormone secreted by pancreatic beta cells that is essential for maintaining glucose homeostasis. Although its peripheral effects have been elucidated in detail, its effect on cognitive function is unclear. The effect of insulin on long-term depression (LTD) of the hippocampus was examined in this study. Method: In this study, 24 male Wistar rats weighing between 200-300 g were used. Rats were divided into four groups as saline-infused group (SF, n=6), insulin infused group (Insulin, n=6), the NT157-infused group (NT157, n=6), and insulin+NT157-infused group (Insulin+NT157, n=6). Long-term depression (LTD) was induced by 900 low-frequency stimuli (LFS) at 1 Hz applied to the perforant pathway. Excitatory postsynaptic potential (EPSP) slope and population spike (PS) amplitudes were recorded from field potentials obtained from dentate gyrus granule cells. At the end of the experiment, PI3K, AKT, GSK3-b, IRS, and MAPT gene expression levels were measured by PCR in the stimulated hippocampi. Results: After stimulation of the perforant path with 1 Hz, PS values showed a statistically significant decrease in the insulin-infused group compared to the SF-infused group (p<0.05). This depression was abolished in the NT157-infused group. AKT mRNA levels decreased in the insulin+NT157 group, whereas IRS mRNA levels increased in the NT157-infused group (p<0.001). GSK3-b mRNA levels were found to be increased in the insulin-infused group. Conclusion: Field potentials recorded from hippocampal granule cells indicated that insulin facilitates LTD in the hippocampus. Understanding the effect of insulin on the hippocampus is necessary to elucidate the relationship between metabolic and degenerative diseases.

Anahtar Kelimeler

• Insulin
• Hippocampus
• NT157
• Synaptic plasticity

İnsülinin Sinaptik Plastisitedeki Rolü: Uzun Dönemli Baskılanma

Öz

Giriş: İnsülin, pankreatik beta hücrelerinden salgılanan glukoz homeostazisinin sürdürülmesinde gerekli bir hormondur. Periferik etkileri ayrıntılı bir şekilde açığa çıkarılmasına rağmen kognitif fonksiyonlar üzerine etkisi belirsizdir. Bu çalışmada insülinin hipokampal uzun dönemli baskılanma üzerine etkisi araştırılmıştır. Metot: Bu çalışmada ağırlıkları 200-300 gr arasında değişen 24 adet Wistar erkek sıçan kullanılmıştır. Sıçanlar; Serum fizyolojik infüze edilen grup (SF, n=6), insülin infüze edilen grup (İnsülin, n=6), NT157 infüze edilen grup (NT157, n=6) ve insülin ile birlikte NT157 infüze edilen grup (İnsülin+NT157, n=6) olmak üzere dört gruba ayrılmıştır. Uzun dönemli baskılanma perforant yola uygulanan 1 Hz 900 adet düşük frekanslı uyarı (DFU) ile indüklenmiştir. Dentat girus granül hücrelerinden elde edilen alan potansiyellerinden eksitatör postsinaptik potansiyel (EPSP) eğimi ve populasyon spike (PS) genlikleri kaydedilmiştir. Deney bitiminde çıkarılan uyarılmış hipokampüslerde PI3K, AKT, GSK3-b, IRS ve MAPT gen ekspresyonu düzeyleri PCR yöntemi ile ölçülmüştür. Bulgular: Perforan yolun 1 Hz ile uyarımı sonrası PS değerleri insülin infüze edilen grupta SF infüze edilen gruba karşı istatistiksel olarak anlamlı düşüş göstermiştir (p<0,05). NT157 infüze edilen grupta bu baskılanma ortadan kalkmıştır. İnsülin+NT157 verilen grupta AKT mRNA seviyeleri azalma göstermiş, NT157 infüze edilen grupta IRS mRNA seviyeleri artmıştır (p<0,001). Yalnızca insülin infüze edilen grupta GSK3-b mRNA seviyeleri artmış bulunmuştur. Sonuç: Hipokampal granül hücrelerinden kaydedilen alan potansiyelleri değerleri, insülinin hipokampüste UDB’ yi kolaylaştırdığını göstermiştir. İnsülinin hipokampüs üzerine etkisinin anlaşılması metabolik ve dejeneratif hastalıklar arasındaki ilişkinin ortaya konması için gereklidir.

Anahtar Kelimeler

• İnsülin
• Hipokampüs
• NT157
• Sinaptik plastisite

Kaynakça

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