Department of Biotechnology, University of Ribeirão Preto, Ribeirão Preto, São Paulo, Brazil.
Department of Biotechnology, University of Ribeirão Preto, Ribeirão Preto, São Paulo, Brazil; School of Medicine, University of Ribeirão Preto, Ribeirão Preto, São Paulo, Brazil.
Life Sci. 2020 Jan 1;240:117072. doi: 10.1016/j.lfs.2019.117072. Epub 2019 Nov 18.
Deficits in cognitive functions are often observed in epileptic patients, particularly in temporal lobe epilepsy (TLE). Evidence suggests that this cognitive decline can be associated with the occurrence of focal brain lesions, especially on hippocampus and cortex regions. We previously demonstrated that the erythrinian alkaloids, (+)-erythravine and (+)-11α-hydroxy-erythravine, inhibit seizures evoked in rats by different chemoconvulsants.
The current study evaluated if these alkaloids would be acting in a neuroprotective way, reducing hippocampal sclerosis, and consequently, improving learning/memory performance.
Here we confirmed the anticonvulsant effect of both alkaloids by means of the pilocarpine seizure-induced model and also showed that they enhanced spatial learning of rats submitted to the Morris Water Maze test reverting the cognition deficit. Additionally, immunohistochemistry assays showed that neuronal death and glial activation were prevented by the alkaloids in the hippocampus CA1, CA3 and dentate gyrus regions at both hemispheres indistinctly 15 days after status epilepticus induction.
Our results show, for the first-time, the improvement on memory/learning elicited by these erythrinian alkaloids. Furthermore, data presented herein explain, at least partially, the cellular mechanism of action of these alkaloids. Together, (+)-erythravine and (+)-11α-hydroxy-erythravine seem to be a promising protective strategy against TLE, comprising three main aspects: neuroprotection, control of epileptic seizures and cognitive improvement.
Moreover, our findings on neuroprotection corroborate the view that seizure frequency and severity, hippocampal lesions and memory deficits are interconnected events.
癫痫患者常出现认知功能障碍，尤其是颞叶癫痫（TLE）。有证据表明，这种认知能力下降可能与局灶性脑损伤有关，尤其是海马体和皮质区域。我们之前已经证明，血根碱类生物碱（+）-血根碱和（+）-11α-羟基血根碱可抑制不同化学惊厥剂诱发的大鼠癫痫发作。
本研究评估了这些生物碱是否具有神经保护作用，是否能减少海马硬化，从而改善学习/记忆能力。
在这里，我们通过匹罗卡品癫痫发作模型证实了这两种生物碱的抗惊厥作用，并表明它们增强了接受水迷宫测试的大鼠的空间学习能力，逆转了认知缺陷。此外，免疫组织化学检测表明，生物碱可防止癫痫持续状态诱导后 15 天左右海马体 CA1、CA3 和齿状回区的神经元死亡和神经胶质激活。
我们的研究结果首次表明，这些血根碱类生物碱可改善记忆/学习能力。此外，本文介绍的数据至少部分解释了这些生物碱的作用机制。总之，（+）-血根碱和（+）-11α-羟基血根碱似乎是一种有前途的 TLE 保护策略，包括三个主要方面：神经保护、控制癫痫发作和认知改善。
此外，我们关于神经保护的发现证实了癫痫发作频率和严重程度、海马体损伤和记忆缺陷是相互关联的事件的观点。
