l-DOPA-induced dyskinesia and neuroinflammation: do microglia and astrocytes play a role?
l-DOPA-induced dyskinesia and neuroinflammation: do microglia and astrocytes play a role?
复制标题
DOI：
10.1111/ejn.13482
复制
发表时间：
2017-01-01
影响因子：
3.4
通讯作者：
Del-Bel, Elaine
中科院分区：
文献类型：
--
作者：
Carta, Anna R.;Mulas, Giovanna;Del-Bel, Elaine
在帕金森病（PD）中，左旋多巴治疗导致出现运动并发症，包括左旋多巴诱导的运动障碍（LID）。LID依赖于一系列突触前和突触后神经元事件，导致皮质纹状体神经传递异常和纹状体投射神经元的适应不良变化。近年来，已提出其他非神经元机制有助于LID。在这些机制中，相当多的注意力集中在左旋多巴诱导的炎症反应。小胶质细胞和星形胶质细胞是神经炎症反应的主要参与者，它们在免疫和神经生理反应之间的界面上的双重作用开始被阐明。小胶质细胞和星形胶质细胞都表达多种神经递质受体，并通过释放几种可溶性分子来调节神经元网络中的突触功能。在这里，我们回顾临床前和临床证据胶质细胞过度激活左旋多巴，支持小胶质细胞和星形胶质细胞在LID的发展中的作用。我们认为，在PD中，慢性和异常激活的小胶质细胞和星形胶质细胞导致异常的神经元-胶质细胞通讯，影响突触活动和神经可塑性，从而促进LID的发展。
In Parkinson's disease (PD), l-DOPA therapy leads to the emergence of motor complications including l-DOPA-induced dyskinesia (LID). LID relies on a sequence of pre- and postsynaptic neuronal events, leading to abnormal corticostriatal neurotransmission and maladaptive changes in striatal projection neurons. In recent years, additional non-neuronal mechanisms have been proposed to contribute to LID. Among these mechanisms, considerable attention has been focused on l-DOPA-induced inflammatory responses. Microglia and astrocytes are the main actors in neuroinflammatory responses, and their double role at the interface between immune and neurophysiological responses is starting to be elucidated. Both microglia and astrocytes express a multitude of neurotransmitter receptors and via the release of several soluble molecules modulate synaptic function in neuronal networks. Here we review preclinical and clinical evidence of glial overactivation by l-DOPA, supporting a role of microglia and astrocytes in the development of LID. We propose that in PD, chronically and abnormally activated microglia and astrocytes lead to an aberrant neuron-glia communication, which affect synaptic activity and neuroplasticity contributing to the development of LID.