Syntaxin 1B Mediates Berberine's Roles in Epilepsy-Like Behavior in a Pentylenetetrazole-Induced Seizure Zebrafish Model

Epilepsy is a neuronal dysfunction syndrome characterized by transient and diffusely abnormal discharges of neurons in the brain. Previous studies have shown that mutations in the syntaxin 1b (stx1b) gene cause a familial, fever-associated epilepsy syndrome. It is unclear as to whether the stx1b gene also correlates with other stimulations such as flashing and/or mediates the effects of antiepileptic drugs. In this study, we found that the expression of stx1b was present mainly in the brain and was negatively correlated with seizures in a pentylenetetrazole (PTZ)-induced seizure zebrafish model. The transcription of stx1b was inhibited by PTZ but rescued by valproate, a broad-spectrum epilepsy treatment drug. In the PTZ-seizure zebrafish model, stx1b knockdown aggravated larvae hyperexcitatory swimming and prompted abnormal trajectory movements, particularly under lighting stimulation; at the same time, the expression levels of the neuronal activity marker gene c-fos increased significantly in the brain. In contrast, stx1b overexpression attenuated seizures and decreased c-fos expression levels following PTZ-induced seizures in larvae. Thus, we speculated that a deficiency of stx1b gene expression may be related with the onset occurrence of clinical seizures, particularly photosensitive seizures. In addition, we found that berberine (BBR) reduced larvae hyperexcitatory locomotion and abnormal movement trajectory in a concentration-dependent manner, slowed down excessive photosensitive seizure-like swimming, and assisted in the recovery of the expression levels of STX1B. Under the downregulation of STX1B, BBR's roles were limited: specifically, it only slightly regulated the levels of the two genes stx1b and c-fos and the hyperexcitatory motion of zebrafish in dark conditions and had no effect on the overexcited swimming behavior seen in conjunction with lighting stimulation. These findings further demonstrate that STX1B protein levels are negatively correlated with a seizure and can decrease the sensitivity of the photosensitive response in a PTZ-induced seizure zebrafish larvae; furthermore, STX1B may partially mediate the anticonvulsant effect of BBR. Additional investigation regarding the relationship between STX1B, BBR, and seizures could provide new cues for the development of novel anticonvulsant drugs.