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