Cullheim Staffan, Thams Sebastian
Department of Neuroscience, Retzius v 8, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Brain Res Rev. 2007 Aug;55(1):89-96. doi: 10.1016/j.brainresrev.2007.03.012. Epub 2007 Apr 19.
Microglia are the resident inflammatory cells of the central nervous system (CNS) extending a network of processes in the CNS parenchyma. Following axon lesion to neurons, most extensively studied in motoneurons, there is a typical retrograde response at the cell body level, including the removal or 'stripping' of synapses from the perikaryon and dendrites of affected cells. Microglia have been attributed a main and active role in this process, although also an involvement of activated astrocytes has been suggested. The signaling pathways for this 'synaptic stripping' have so far been unknown, but recently some classical immune recognition molecules, the MHC class I molecules, have been shown to have a strong influence on the strength and pattern of the synapse elimination response. Since there is an expression of MHC class I in both neurons and glia, in particular microglia, as well as MHC class I related receptors in axons and microglia, there are good reasons to believe that classical immune recognition signaling between neurons and glia underlies part of the 'stripping' response. A role for microglia in an interplay with synapses based on this type of signaling is further exemplified by the fact that, in the absence of some MHC class I related receptors normally found on microglia during development, profound effects on synaptic function and biochemistry have been demonstrated. Such effects may be linked to the development of various disorders of the CNS, such as degenerative disease.
小胶质细胞是中枢神经系统（CNS）中的常驻炎性细胞，在CNS实质中延伸出一个过程网络。在轴突损伤神经元后，在运动神经元中对此进行了最广泛的研究，在细胞体水平上存在典型的逆行反应，包括从受影响细胞的核周体和树突上去除或“剥离”突触。小胶质细胞在这一过程中被认为起主要和积极的作用，尽管也有人提出活化的星形胶质细胞也参与其中。到目前为止，这种“突触剥离”的信号通路尚不清楚，但最近一些经典的免疫识别分子，即MHC I类分子，已被证明对突触消除反应的强度和模式有强烈影响。由于神经元和胶质细胞，特别是小胶质细胞中都有MHC I类的表达，以及轴突和小胶质细胞中有MHC I类相关受体，因此有充分的理由相信神经元和胶质细胞之间的经典免疫识别信号是“剥离”反应的部分基础。小胶质细胞在基于这种信号传导与突触相互作用中的作用进一步体现在以下事实上：在发育过程中，小胶质细胞通常不存在一些MHC I类相关受体的情况下，已证明对突触功能和生物化学有深远影响。这种影响可能与中枢神经系统的各种疾病的发展有关，如退行性疾病。
