This study aims to validate our hypothesis that acid-sensing ion channels （ASICs） may contribute to the symptom of pain in patients with chronic prostatitis （CP）. We first established a CP rat model, then isolated...This study aims to validate our hypothesis that acid-sensing ion channels （ASICs） may contribute to the symptom of pain in patients with chronic prostatitis （CP）. We first established a CP rat model, then isolated the L5-S2 spinal dorsal horn neurons for further studies. ASICla was knocked down and its effects on the expression of neurogenic inflammation-related factors in the dorsal horn neurons of rat spinal cord were evaluated. The effect of ASICla on the Ca2＋ ion concentration in the dorsal horn neurons of rat spinal cord was measured by the intracellular calcium （[Ca~＊]i） intensity. The effect of ASICla on the p38/mitogen-activated protein kinase （MAPK） signaling pathway was also determined. ASICla was significantly upregulated in the CP rat model as compared with control rats. Acid-induced ASICla expression increased [Ca2＋]i intensity in the dorsal horn neurons of rat spinal cord. ASICla also increased the levels of neurogenic inflammation-related factors and p-p38 expression in the acid-treated dorsal horn neurons. Notably, ASICla knockdown significantly decreased the expression of pro-inflammatory cytokines. Furthermore, the levels of p-p38 and pro-inflammatory cytokines in acid-treated dorsal horn neurons were significantly decreased in the presence of PcTx-1, BAPTA-AM, or SB203580. Our results showed that ASIC1a may contribute to the symptom of pain in patients with CP, at least partially, by regulating the p38/MAPK signaling pathway.展开更多
生理水平的质子在生物体内分布广泛,具有重要的生理功能。在特定的病理条件下,正常的酸碱平衡被破坏,导致质子大量生成和累积,产生对机体有害的酸毒(acidotoxicity)。组织酸化是多种神经系统疾病(如缺血性中风、多发性硬化症以及亨廷顿...生理水平的质子在生物体内分布广泛,具有重要的生理功能。在特定的病理条件下,正常的酸碱平衡被破坏,导致质子大量生成和累积,产生对机体有害的酸毒(acidotoxicity)。组织酸化是多种神经系统疾病(如缺血性中风、多发性硬化症以及亨廷顿舞蹈症等)的共同病理特征,也是致这些疾病神经损伤的原因之一。质子可直接激活酸敏感离子通道(acid-sensing ion channel,ASIC),介导组织酸化相关的生理和病理功能,例如,缺血性神经损伤。一直以来,ASIC引起酸毒性神经损伤被认为主要依赖于通道介导的细胞内钙离子升高。然而,本研究组新近的研究表明ASIC1a亚型通道能够通过激活受体相互作用蛋白1(receptor-interacting protein 1,RIP1),介导不依赖于通道离子通透功能的细胞程序性坏死。另外,亚细胞定位研究发现,除了在神经元膜表面,ASIC1a还可以定位在线粒体内膜上,通过调控线粒体通透性转变(mitochondrial permeability transition,MPT)过程,在缺血性神经损伤中发挥重要作用。这些进展使人们对于ASIC介导神经元死亡的机制有了新的认识。展开更多
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...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。展开更多
基金This research was supported in part by grants from the National Natural Science Foundation of China （No. 81400757） National College Students Innovation and Entrepreneurship Training Program （No. 201510366009） and Anhui Provincial Natural Science Foundation （1508085QH 171 ）.
文摘This study aims to validate our hypothesis that acid-sensing ion channels （ASICs） may contribute to the symptom of pain in patients with chronic prostatitis （CP）. We first established a CP rat model, then isolated the L5-S2 spinal dorsal horn neurons for further studies. ASICla was knocked down and its effects on the expression of neurogenic inflammation-related factors in the dorsal horn neurons of rat spinal cord were evaluated. The effect of ASICla on the Ca2＋ ion concentration in the dorsal horn neurons of rat spinal cord was measured by the intracellular calcium （[Ca~＊]i） intensity. The effect of ASICla on the p38/mitogen-activated protein kinase （MAPK） signaling pathway was also determined. ASICla was significantly upregulated in the CP rat model as compared with control rats. Acid-induced ASICla expression increased [Ca2＋]i intensity in the dorsal horn neurons of rat spinal cord. ASICla also increased the levels of neurogenic inflammation-related factors and p-p38 expression in the acid-treated dorsal horn neurons. Notably, ASICla knockdown significantly decreased the expression of pro-inflammatory cytokines. Furthermore, the levels of p-p38 and pro-inflammatory cytokines in acid-treated dorsal horn neurons were significantly decreased in the presence of PcTx-1, BAPTA-AM, or SB203580. Our results showed that ASIC1a may contribute to the symptom of pain in patients with CP, at least partially, by regulating the p38/MAPK signaling pathway.
基金supported by grants from the National Basic Research Development Program of China(No.2014CB910300)the National Natural Science Foundation of China(No.31461143004)
文摘生理水平的质子在生物体内分布广泛,具有重要的生理功能。在特定的病理条件下,正常的酸碱平衡被破坏,导致质子大量生成和累积,产生对机体有害的酸毒(acidotoxicity)。组织酸化是多种神经系统疾病(如缺血性中风、多发性硬化症以及亨廷顿舞蹈症等)的共同病理特征,也是致这些疾病神经损伤的原因之一。质子可直接激活酸敏感离子通道(acid-sensing ion channel,ASIC),介导组织酸化相关的生理和病理功能,例如,缺血性神经损伤。一直以来,ASIC引起酸毒性神经损伤被认为主要依赖于通道介导的细胞内钙离子升高。然而,本研究组新近的研究表明ASIC1a亚型通道能够通过激活受体相互作用蛋白1(receptor-interacting protein 1,RIP1),介导不依赖于通道离子通透功能的细胞程序性坏死。另外,亚细胞定位研究发现,除了在神经元膜表面,ASIC1a还可以定位在线粒体内膜上,通过调控线粒体通透性转变(mitochondrial permeability transition,MPT)过程,在缺血性神经损伤中发挥重要作用。这些进展使人们对于ASIC介导神经元死亡的机制有了新的认识。
文摘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。
