Sun Can, Fu Jian, Qu Zhenzhen, Jia Lijing, Li Dongxiao, Zhen Junli, Wang Weiping
Key Laboratory of Neurology of Hebei Province, Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
Department of Neurology, Peking University Third Hospital, Beijing, China.
Front Mol Neurosci. 2021 Jan 20;13:617143. doi: 10.3389/fnmol.2020.617143. eCollection 2020.
Epilepsy is a complex neurological disorder with frequent psychiatric, cognitive, and social comorbidities in addition to recurrent seizures. Cognitive impairment, one of the most common comorbidities, has severe adverse effects on quality of life. Chronic intermittent hypobaric hypoxia (CIHH) has demonstrated neuroprotective efficacy in several neurological disease models. In the present study, we examined the effects of CIHH on cognition and hippocampal function in chronic epileptic rats. CIHH treatment rescued deficits in spatial and object memory, hippocampal neurogenesis, and synaptic plasticity in pilocarpine-treated epileptic rats. The Wnt/β-catenin pathway has been implicated in neural stem cell proliferation and synapse development, and Wnt/β-catenin pathway inhibition effectively blocked the neurogenic effects of CIHH. Our findings indicate that CIHH rescues cognitive deficits in epileptic rats Wnt/β-catenin pathway activation. This study establishes CIHH and Wnt/β-catenin pathway regulators as potential treatments for epilepsy- induced cognitive impairments.
癫痫是一种复杂的神经系统疾病,除了反复发作的癫痫外,还常伴有精神、认知和社会方面的共病。认知障碍是最常见的共病之一,对生活质量有严重的不良影响。慢性间歇性低压缺氧(CIHH)已在多种神经疾病模型中显示出神经保护作用。在本研究中,我们研究了CIHH对慢性癫痫大鼠认知和海马功能的影响。CIHH治疗可挽救毛果芸香碱诱导的癫痫大鼠的空间和物体记忆缺陷、海马神经发生及突触可塑性。Wnt/β-连环蛋白通路与神经干细胞增殖和突触发育有关,抑制Wnt/β-连环蛋白通路可有效阻断CIHH的神经发生作用。我们的研究结果表明,CIHH通过激活Wnt/β-连环蛋白通路挽救癫痫大鼠的认知缺陷。本研究确立了CIHH和Wnt/β-连环蛋白通路调节剂作为癫痫所致认知障碍的潜在治疗方法。