Investigation of The Effects of Endogenous BDNF on Kainic Acid Induced Seizures

Year 2023, Volume: 2 Issue: 1, 8 - 15, 30.03.2023

Selcen Abidin , Hatice Keser , Elif Şahin , Ahmet Alver , İsmail Abidin

Abstract

Brain derived neurotrophic factor (BDNF), a major mediator of plasticity in the central nervous system. Due to fast synaptic actions of BDNF, it is thought to be a modulator of excitability in neuronal circuitry. There is a two sided relationship between BDNF and epileptic activity. BDNF levels increase following seizure or kainate administration. Additionally, BDNF administration causes hyperexcitability. BDNF deficiency attenuates seizures or epileptiform activity in several epilepsy models. In this study, our aim was to investigate modulatory effects of reduced endogenous BDNF on kainic acid (KA) induced seizures. For this purpose, BDNF heterozygous mice and their wild type littermates were compared. Animals were injected intraperitoneally with either vehicle (0.9% saline) or kainic acid (15 mg/kg). Four groups were formed: vehicle injected wild type (WT-SA; n=9) and BDNF heterozygous mice (HT-SA; n=9), kainic acid injected wild type (WT-KA, n=10) and BDNF heterozygous mice (HT-KA, n=10). Racine scorings were determined for 5 min epochs from the video recordings. In the hippocampal tissue synaptic markers proteins synaptophysin (SYP), post-synaptic density (PSD-95) and inflammatory markers interleukin-6 (IL-6) and tumor necrosis factor Alpha (TNF-α) were measured. Besides, oxidative stress parameters were evaluated. WT-KA group’s score were higher at 20 and 25 min than that of HT-KA group (p<0.05). MDA levels were higher in kainic groups (p<0.05). Kainic acid did not affect neuroinflammation and synaptic proteins significantly. Our results showed that reduced BDNF temporarily posed a resistance against seizure but intact levels of BDNF failed to protect against oxidative stress in kainic acid model.

Keywords

kainic acid, epilepsy, synaptic proteins, oxidative stress

Thanks

The authors wish to thank Sait Al and Ibrahim Aydin from Surgical Practice Research Center of Karadeniz Technical University for professional assistance with the experimental studies.

Endojen BDNF'ün Kainik Asit Kaynaklı Nöbetler Üzerindeki Etkilerinin İncelenmesi

Abstract

Beyin kaynaklı nörotrofik faktör (BDNF), merkezi sinir sisteminde plastisitede rol oynayan önemli bir aracıdır. BDNF'nin hızlı sinaptik etkileri nedeniyle, nöronal devrede uyarılabilirliği düzenlediği düşünülmektedir. BDNF ile epileptik aktivite arasında iki yönlü bir ilişki vardır. Nöbet veya kainat uygulamasını takiben BDNF seviyeleri yükselir. Bunun yanında, BDNF uygulaması aşırı uyarılabilirliğe neden olur. BDNF eksikliği, birkaç epilepsi modelinde nöbetleri veya epileptiform aktiviteyi azaltır. Bu çalışmada amacımız, azaltılmış endojen BDNF'nin kainik asit (KA) kaynaklı nöbetler üzerindeki modülatör etkilerini araştırmaktı. Bu amaçla BDNF heterozigot fareler ve bunların yabani tip yavruları karşılaştırıldı. Hayvanlara %0.9’luk tuzlu su çözeltisi veya kainik asit (15 mg/kg) intraperitoneal olarak verildi. Dört grup oluşturuldu: tuzlu su enjekte edilen yabani tip fareler (WT-SA; n=9) ve BDNF heterozigot fareler (HT-SA; n=9), kainik asit enjekte edilen yabani tip (WT-KA, n=10) ve BDNF heterozigot fareler (HT-KA, n=10). Video kayıtlarından 5 dakikalık dönemler için Racine skorları belirlendi. Hipokampal dokuda, sinaptik proteinler sinaptofizin (SYP) ve PSD-95’in yanında inflamatuar belirteçler interlökin-6 (IL-6) ve tümör nekroz faktörü alfa (TNF-α) ölçüldü. Ayrıca oksidatif stres parametreleri değerlendirildi. WT-KA grubunun skoru 20 ve 25. dakikada HT-KA grubuna göre daha yüksekti (p<0.05). MDA düzeyleri kainik gruplarda daha yüksekti (p<0.05). Kainik asit, nöroinflamasyonu ve sinaptik proteinleri önemli ölçüde etkilemedi. Sonuçlarımız, azalmış BDNF'nin geçici olarak nöbete karşı bir direnç oluşturduğunu, ancak normal BDNF düzeylerinin kainik asit modelinde oksidatif strese karşı koruma sağlamadığını gösterdi.

Keywords

BDNF, kainik asit, epilepsi, sinaptik proteinler, oksidatif stres, kainic acid, epilepsy, synaptic proteins, oxidative stress

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