Bilge Guvenc TUNA, Yavuz YAVUZ, Gamze KUKU, Akif MAHARRAMOV, Bayram YİLMAZ, Melike SARİCAM, Merve ERCAN, Mustafa CULHA, Soner DOGAN

Modifiye altın nanoparçacıkların fare hipokampal kesitlerindeki nöronal fonksiyonlar üzerine etkileri

Amaç: Altın nanoparçacık (AuNP) modifikasyonlarının sinir sistemi fonksiyonunu nasıl etkileyebileceği tam olarak bilinmemektedir. Bu çalışmada, AuNp’lerin glikoz (GlikozAuNp), oligonükleotid (15 baz, d(A)15AuNP) veya peptid (negatif amino asit içeren, AspAuNp) ile işlevselleştirilmiş formlarının fare hipokampal nöronları üzerindeki biyoelektriksel etkisinin ex vivo olarak araştırılması amaçlanmıştır. Yöntem: AuNP modifikasyonları UV/Vis spektroskopi, Dinamik Işık Saçılması (DLS) ve Geçirimli Elektron Mikroskobu (TEM) ile karakterize edildi ve ex vivo olarak 4-6 haftalık Balb-c erkek farelerin beyin hipokampüs bölgelerinden alınan kesitlere eklendi, spontan ve uyarılmış aksiyon potansiyelleri (AP) yama kıskacı, tüm hücre tekniği ile kaydedildi. Spontan AP’lerinin en büyük genlik değeri, yükselen eğimi, yarı genişliği, iki pik arasında geçen süre ve ateşleme hızı analiz edildi. Bulgular: Karakterizasyon sonuçları AuNP’lerin yüzey modifikasyonlarının 5-7 nm çapında ve koloidal olduğunu gösterdi. Spontan AP’lerin ateşleme hızı GlikozAuNp (n=9) gurubunda, kontrol (n=9), AspAuNp (n=6) ve d(A)15AuNP (n=9) eklenen gruplara göre en fazla olarak ölçüldü (sırasıyla 10.1±5.5 4.4±3.2 9.5±3.8 ve 6.2±3.0 pik/s, p>0.05). Ek olarak, uyarılmış AP’lerin özelliklerini yansıtan akım voltaj (I-V) analizinde, GlikozAuNp (n=8) gurubunun akım uyarılarına ((-150)–(+150 pA)) cevaben oluşturdukları membran potansiyelleri kontrol (n=8) ve d(A)15AuNP (n=9) gruplarının cevabına göre negatif akım bölgesinde negatife, pozitif akım uyarısı bölgesinde pozitife kaydı. Sonuç: Medikal uygulamalarda kullanılacak AuNP’lerin yüzey modifikasyonlarının hipokampal nöronların AP’lerinin ateşleme hızını arttırarak, patolojik koşulları tetikleyebilecekleri ve daha biyouyumlu formların belirlenmesi gerektiği önerilebilir.

Anahtar Kelimeler:

Altın nanoparçacıklar, aksiyon potansiyeli, Yüzey modifikasyonları

The effect of modified gold nanoparticles on the function of neurons of mice hipocampal brain slices

Aim: It is still unclear whether modifications of gold nanoparticles (AuNp) affect the function of the nervous system. Aim of this study was to investigate the bioelectrical effect of glucose (GlucoseAuNp), oligonükleotite (d(A)15AuNP) or peptide (AspAuNp) modified AuNp, on hippocampal mouse neurons after ex vivo administration. Methods: AuNP modifications were characterized by UV/Vis spectroscopy, Dynamic Light Scattering (DLS) and Transmission Electron Microscopy (TEM). Subsequently, AuNp modifications were added ex vivo to sections of hippocampal regions obtained from the brains of 4-6 week old male Balb-c mice, and then spontaneous and stimulated action potentials (AP) were recorded by patch clamp with whole-cell technique. The Peak amplitude, rising slope, half with and firing rate of Aps were analyzed. Results: Characterization results showed that AuNp modifications have 5-7 nm size and colloidal shape. The firing rate of the APs measured in the GlucoseAuNp (n=9) group was higher compared to the AspAuNp (n=7), d(A)15AuNP (n=9), and control (n=9) groups (respectively 10.1±5.5 9.5±3.8, 6.2±3.0 pic/s, and 4.4±3.2, pic/s, p>0.05). In addition, current voltage (I-V) analysis showed that the membrane potential in response to current stimuli ((-150)–(150 pA)) of the GlucoseAuNp (n=8) shifted negative for negative current stimulations and positive for positive current stimulations compared to the control (n=8) and d(A)15AuNP (n=9) groups. Conclusion: The surface AuNp modifications will be used in medical applications might increase the firing rate of Aps and stimulate neurological patholojies in hippocampal neurons and it may be suggested that more biocompatible AuNp forms should be identified.

Keywords:

Gold nanoparticles, Action potential, Surface Modifications,

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