Antibody-mediated impairment and homeostatic plasticity of autonomic ganglionic synaptic transmission.

Antibody-mediated impairment and homeostatic plasticity of autonomic ganglionic synaptic transmission.
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DOI:
10.1016/j.expneurol.2009.12.016
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发表时间:
2010-03
影响因子:
5.3
通讯作者:
Vernino, Steven
Vernino, Steven
中科院分区:
医学2区
文献类型:
--
作者:
Wang, Zhengbei;Low, Phillip A.;Vernino, Steven

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抗神经节乙酰胆碱受体(AChR)抗体被认为是自身免疫性自主神经节病(AAG)的原因。为了研究AAG动物模型中神经节的神经传递,记录了小鼠颈上神经节(SCG)神经元的诱发和自发兴奋性突触后电位(EPSP)。在体外,神经节暴露于AAG患者的免疫球蛋白,逐渐抑制突触传递。被动转移抗体后,诱发的EPSP波幅降低,部分神经元无突触反应。尽管神经节细胞AChR抗体在小鼠血清中持续存在,EPSP波幅在第7天恢复。与抗体介导的突触后AChR的降低一致,小型EPSP波幅有更持续的降低(至少14天)。虽然量子大小减小了,但自发突触事件发生的频率逐渐增加,这表明突触前效能的代偿性增加。量子大小在21天后恢复到基线水平,而频率至少在四周内保持增加。神经节AChR抗体导致自主神经节突触传递功能障碍。自主神经传递的动态平衡可塑性有助于解释一些AAG患者的自发临床恢复,也可能在调节正常的自主神经反射方面发挥重要作用。
Antibodies against ganglionic acetylcholine receptors (AChR) are implicated as the cause of autoimmune autonomic ganglionopathy (AAG). To characterize ganglionic neurotransmission in an animal model of AAG, evoked and spontaneous excitatory post-synaptic potentials (EPSP) were recorded from neurons in isolated mouse superior cervical ganglia (SCG). In vitro exposure of ganglia to IgG from AAG patients progressively inhibited synaptic transmission. After passive transfer of antibody to mice, evoked EPSP amplitude decreased, and some neurons showed no synaptic responses. EPSP amplitude recovered by day seven despite persistence of ganglionic AChR antibody in the mouse serum. There was a more persistent (at least 14 day) reduction in miniature EPSP amplitude consistent with antibody-mediated reduction in post-synaptic AChR. Although the quantal size was reduced, a progressive increase in the frequency of spontaneous synaptic events occurred, suggesting a compensatory increase in presynaptic efficacy. The quantal size returned to baseline by 21 days while the frequency remained increased for at least four weeks. Ganglionic AChR antibodies cause an impairment of autonomic ganglionic synaptic transmission. Homeostatic plasticity in autonomic neurotransmission could help explain the spontaneous clinical recovery seen in some AAG patients and may also play an important role in regulating normal autonomic reflexes.
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