《生命科学》 2017, 29(11): 1167-1173
摘 要：摘 要：复发性癫痫诱导慢性树突棘重塑对癫痫发生、终止和长期认知变化很关键，但是调控树突棘重塑的机制并不十分清楚。研究表明，癫痫发作时细胞外[H+]i 增加导致组织酸中毒，激活酸敏感离子通道(acid-sensing ion channels， ASICs)，引起慢性树突棘重塑。现总结酸中毒和酸敏感离子通道亚型ASIC1a 在复发性癫痫引起的树突棘重塑中的作用，重点分析了酸中毒过程的时空变化对痫样放电和树突棘重塑可能的影响，以及酸中毒与ASIC1a 在兴奋性和抑制性神经元的功能表达之间的关系，认为ASIC1a 可能通过不同机制介导酸中毒在癫痫发生和持续阶段对树突棘的影响。未来研究需要进一步探索癫痫引起的慢性神经元结构和功能改变，阐明酸中毒和ASIC1a 在癫痫及其引起的树突棘缺失中的作用。
Abstract: Abstract: It is well known that recurrent seizures induce spine loss， which may be critical for epileptogenesis， seizure termination， or long-term cognitive changes. However， the mechanisms that regulate spine remodeling in epilepsy remain not entirely clear. Researches have demonstrated that recurrent seizures generate acidosis， or a decrease in extracellular brain pH value. ASIC1a plays a particularly important role in acid-sensing in the brain. This article summarizes the recent progress related to this issue based on the work in our lab and others， elucidates the underlying molecular mechanisms. We suggest that acidosis has differential effects on network excitability at different stages during seizure progression. The effect of H+ on pyramidal neurons and interneurons is determined by both the amplitude and location of acidosis during epileptiform activity (EA). During seizure onset， H+ primarily activates pyramidal neurons and facilitates EA. At later stages， when acidosis becomes global， H+ activates inhibitory circuits and contributes to seizure termination. The future study should investigate the role of H+ in seizure progression with an emphasis on seizure-induced spine loss， which has potentially important implications in epileptogenesis and seizure progression as well as understanding chronic effects of epilepsy.
