Neuroscience Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Bengaluru 560064, India.
Molecular Reproduction, Development and Genetics (MRDG), Indian Institute of Science, Bengaluru 560012, India.
Int J Mol Sci. 2022 Sep 16;23(18):10807. doi: 10.3390/ijms231810807.
Epilepsy, a heterogeneous group of brain-related diseases, has continued to significantly burden society and families. Epilepsy comorbid with neurodevelopmental disorders (NDDs) is believed to occur due to multifaceted pathophysiological mechanisms involving disruptions in the excitation and inhibition (E/I) balance impeding widespread functional neuronal circuitry. Although the field has received much attention from the scientific community recently, the research has not yet translated into actionable therapeutics to completely cure epilepsy, particularly those comorbid with NDDs. In this review, we sought to elucidate the basic causes underlying epilepsy as well as those contributing to the association of epilepsy with NDDs. Comprehensive emphasis is put on some key neurodevelopmental genes implicated in epilepsy, such as , , , and , along with a few others, and the main electrophysiological and behavioral deficits are highlighted. For these genes, the progress made in developing appropriate and valid rodent models to accelerate basic research is also detailed. Further, we discuss the recent development in the therapeutic management of epilepsy and provide a briefing on the challenges and caveats in identifying and testing species-specific epilepsy models.
癫痫是一组异质性的脑部疾病,一直给社会和家庭带来沉重负担。人们认为,癫痫伴发神经发育障碍(NDD)是由于涉及兴奋和抑制(E/I)平衡破坏的多方面病理生理机制引起的,这种破坏会阻碍广泛的功能性神经元回路。尽管该领域最近受到科学界的广泛关注,但研究尚未转化为可行的治疗方法来彻底治愈癫痫,特别是那些伴发 NDD 的癫痫。在这篇综述中,我们试图阐明癫痫的基本原因以及导致癫痫与 NDD 相关的原因。我们全面强调了一些关键的神经发育基因,如、、、和,以及其他一些基因,突出了它们主要的电生理和行为缺陷。对于这些基因,我们详细介绍了为加速基础研究而开发合适和有效的啮齿动物模型方面所取得的进展。此外,我们还讨论了癫痫治疗管理方面的最新进展,并简要介绍了在鉴定和测试特定于物种的癫痫模型方面的挑战和注意事项。