Publication: Transferin modifiyeli altın nanoparçacıkların sinir hücrelerindeki biyoelektriksel etkisinin farelerde araştırılması
Abstract
Amaç: Bu tez çalışmasında altın nanoparçacıkların ve transferin modifikasyonunun fare hipokampal nöron hücrelerinin biyoelektriksel özelliklerine (ex vivo) ve farelerin davranışlarına (in vivo) etkilerinin araştırılması amaçlandı.Gereç ve Yöntem: Bu amaçla 13 nm boyutlu altın nanoparçacıklar ve transferin modifikasyonları sentezlendi ve karakterize edildi. 21 adet (4-6 haftalık) C57BL/ 6 erkek fare in vivo ve ex vivo olmak üzere iki grup olarak belirlendi. Nanoparçacıklar fare hipokampal beyin kesitlerine ex vivo olarak uygulandı ve yama kıskacı yöntemiyle aksiyon potansiyeli akımlarının kayıtları alındı. Ayrıca, nanoparçacıklar 7 gün boyunca her gün farelere intraperitonel olarak enjekte edildikten sonra nanoparçacıkların farelerin anksiyete benzeri (açık alan testi, yükseltilmiş labirent tesiti) ve yeme davranışına etkileri belirlendi.Bulgular: Fare beyin kesitlerine ex vivo olarak uygulanan grupta; kontol grubuna kıyasla çıplak altın nanoparçacıkların, hipokampal nöronlarda oluşturduğu aksiyon potansiyeli spike sayısında ve spontan ateşleme hızında istatistiksel olarak anlamlı artış belirlendi. Transferin kaplı altın nanoparçacıkların ise nöronlarda oluşturduğu spontan ateşleme hızı, kontrol grubu ile benzer sonuçlar gösterdi (p<0,0001; kontrol n=32, Au=n =53, Trans-Au n=61). In vivo grubunda davranış deneylerinde; açık alan ve yükseltilmiş labirent testlerinde ve yeme davranışında gruplar arasında fark belirlenmedi (p>0,05). Sonuçlar: Transferin kaplı altın nanoparçacıkların, hem ex vivo’da fare nöronlarının biyoelektriksel özelliklerinde, hem de in vivo’da farelerde davranış değişikliği göstermediği belirlendiğinden, nöral hastalıklarda hedefe ilaç ve gen taşıması gibi biyoteknolojik komplekslerde kullanılması özellikle tercih edilebileceği söylenebilir.
Purpose: In this thesis, the effect of gold nanoparticles and their transferrin modification on the bioelectrical properties of mouse hippocampal neuron cells (ex vivo) and on the behavior of mice (in vivo) was investigated.Material and Methods: For this purpose, 13 nm gold nanoparticles and their transferrin modifications were synthesized and characterized. 15 (4-6weeks) C57BL/ 6 male mice were assigned into two groups as in vivo and as ex vivo. Nanoparticles were applied on mouse hippocampal brain slices ex vivo and action potential currents were recorded by using patch clamp. Moreover, mice were injected intraperitoneally with nanoparticles daily for 7 days and the effect of nanoparticles on anxiety-like (open field and elevated plus maze test) and feeding behavior of mice were determined.Results: Ex vivo spontaneous action potential currents of hippocampal neurons stimulated by gold nanoparticles had significantly increased the number of spikes and firing rate compared to control neurons. Spontaneous action potential currents of control and transferrin coated nanoparticle groups were similar (p<0.0001; Control n=32, Au =n=53, Trans-Au n=61). In in vivo, anxiety-like (open field and elevated plus maze test) and feeding behavior of mice were not different between the tree groups (p>0.05).Conclusion: Transferrin modified gold nanoparticles did not have any effect on bioelectrical properties of neurons ex vivo and on behavior in vivo, from which it can be concluded that Transferrin modified gold nanoparticles are suggested to be used in biotechnological complexes such as neuronal targeted drug delivery and gene transport to the brain.
Purpose: In this thesis, the effect of gold nanoparticles and their transferrin modification on the bioelectrical properties of mouse hippocampal neuron cells (ex vivo) and on the behavior of mice (in vivo) was investigated.Material and Methods: For this purpose, 13 nm gold nanoparticles and their transferrin modifications were synthesized and characterized. 15 (4-6weeks) C57BL/ 6 male mice were assigned into two groups as in vivo and as ex vivo. Nanoparticles were applied on mouse hippocampal brain slices ex vivo and action potential currents were recorded by using patch clamp. Moreover, mice were injected intraperitoneally with nanoparticles daily for 7 days and the effect of nanoparticles on anxiety-like (open field and elevated plus maze test) and feeding behavior of mice were determined.Results: Ex vivo spontaneous action potential currents of hippocampal neurons stimulated by gold nanoparticles had significantly increased the number of spikes and firing rate compared to control neurons. Spontaneous action potential currents of control and transferrin coated nanoparticle groups were similar (p<0.0001; Control n=32, Au =n=53, Trans-Au n=61). In in vivo, anxiety-like (open field and elevated plus maze test) and feeding behavior of mice were not different between the tree groups (p>0.05).Conclusion: Transferrin modified gold nanoparticles did not have any effect on bioelectrical properties of neurons ex vivo and on behavior in vivo, from which it can be concluded that Transferrin modified gold nanoparticles are suggested to be used in biotechnological complexes such as neuronal targeted drug delivery and gene transport to the brain.