Departament of Biosciences, Universidade Federal de São Paulo, Santos, Brazil.
Departament of Biosciences, Universidade Federal de São Paulo, Santos, Brazil; Department of Pharmacology, Universidade Federal de São Paulo, São Paulo, Brazil.
Neuropeptides. 2022 Feb;91:102209. doi: 10.1016/j.npep.2021.102209. Epub 2021 Nov 16.
Epilepsy is a chronic neuropathology characterized by an abnormal hyperactivity of neurons that generate recurrent, spontaneous, paradoxical and synchronized nerve impulses, leading or not to seizures. This neurological disorder affects around 70 million individuals worldwide. Pharmacoresistance is observed in about 30% of the patients and long-term use of antiepileptics may induce serious side effects. Thus, there is an interest in the study of the therapeutic potential of bioactive substances isolated from natural products in the treatment of epilepsy. Arthropod venoms contain neurotoxins that have high affinity for molecular structures in the neural tissue such as receptors, transporters and ion channels both in glial and neuronal membranes. This study evaluated the potential neuroprotective effect of melittin (MEL), an active compound of bee venom, in the bicuculline-induced seizure model (BIC) in rats. Male Wistar rats (3 months, 250-300 g) were submitted to surgery for the implantation of a unilateral cannula in the lateral ventricle. After the recovery period, rats received a microinjection of saline solution or MEL (0.1 mg per animal). Firstly, rats were evaluated in the open field (20 min) and in the elevated plus maze (5 min) tests after received microinjection of saline or MEL. After, 30 min later animals received BIC (100 mg/ml) or saline, and their behaviors were analyzed for 20 min in the open field according to a seizure scale. At the end, rats were euthanized, brains collected and processed to glial fibrillary acidic protein (GFAP) immunohistochemistry evaluation. No changes were observed in MEL-treated rats in the open field and elevated plus maze. However, 90% of MEL-treated animals were protected against seizures induced by BIC. There was an increase in the latency for the onset of seizures, accompanied by a reduction of GFAP-immunoreactivity cells in the dentate gyrus and CA1. Thus, our study suggests that MEL has an anticonvulsant potential, and further studies are needed to elucidate the mechanisms involved in this action.
癫痫是一种慢性神经病理学疾病，其特征为神经元异常过度活跃，导致反复、自发、反常和同步的神经冲动产生，进而引发或不引发癫痫发作。这种神经系统疾病影响着全球约 7000 万人。大约 30%的患者存在药物抵抗，而长期使用抗癫痫药物可能会引起严重的副作用。因此，人们对从天然产物中分离出的生物活性物质在治疗癫痫方面的治疗潜力产生了兴趣。节肢动物毒液中含有神经毒素，这些毒素对神经组织中的分子结构（如受体、转运体和离子通道）具有高亲和力，这些结构存在于神经胶质和神经元的膜中。本研究评估了蜂毒中一种活性化合物蜂肽（MEL）在双侧颈内动脉结扎致痫大鼠模型（BIC）中的神经保护作用。雄性 Wistar 大鼠（3 个月龄，250-300g）接受了单侧侧脑室插管手术。恢复期后，大鼠接受了生理盐水或 MEL（每只动物 0.1mg）的微量注射。首先，大鼠在接受生理盐水或 MEL 微量注射后进行了旷场（20min）和高架十字迷宫（5min）测试。之后，30min 后，动物接受了 BIC（100mg/ml）或生理盐水，在旷场中分析它们的行为 20min，根据癫痫发作量表进行评估。最后，大鼠被安乐死，收集大脑并进行胶质纤维酸性蛋白（GFAP）免疫组织化学评估。MEL 处理的大鼠在旷场和高架十字迷宫中没有观察到变化。然而，90%的 MEL 处理动物对 BIC 诱导的癫痫发作具有保护作用。发作潜伏期延长，同时齿状回和 CA1 区的 GFAP 免疫反应性细胞减少。因此，我们的研究表明 MEL 具有抗惊厥作用，需要进一步研究来阐明其作用机制。
