A Role for Microglial Cells in Reshaping Neuronal Circuitry of the Adult Rat Auditory Brainstem After Its Sensory Deafferentation
A Role for Microglial Cells in Reshaping Neuronal Circuitry of the Adult Rat Auditory Brainstem After Its Sensory Deafferentation
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DOI：
10.1002/jnr.23334
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发表时间：
2014-04-01
影响因子：
4.2
通讯作者：
Illing, Robert-Benjamin
中科院分区：
文献类型：
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作者：
Janz, Philipp;Illing, Robert-Benjamin
脑干消融触发成年哺乳动物中枢听觉系统的细胞和分子反应，导致听觉脑干细胞网络的复杂重排。小胶质细胞在这些过程中的作用在很大程度上是未知的。我们分析了耳蜗核单侧感觉传入阻滞后1天和7天听性脑干中小胶质细胞的形态学和分子反应以及细胞联系。耳蜗腹侧核（VCN）小胶质细胞的形态学变化明显。在VCN和外侧上上级橄榄（LSO）中，小胶质细胞活化先于星形胶质细胞肥大。在耳蜗消融后早期VCN的轴突变性过程中，p-ERK 1/2和p-p38免疫反应性小胶质细胞表现出肥大的表型，突起部分围绕着谷氨酸能突触，但不围绕GABA能突触。在耳蜗电切后1周VCN神经再支配高峰期，小胶质细胞数量大量增加。小胶质细胞现在显示密集的分支并列Gap 43免疫反应轴突和他们的终端。此外，我们确定了LSO和下丘中小胶质细胞和星形胶质细胞群体的病变依赖性变化。通过covisualizing细胞学标志物，如NeuN，GFAP，CD 11b，vGluT-1，GAD-65，和Gap 43与突出的MAP激酶ERK 1/2和p38，我们表明，MAPK信号传导受小胶质细胞的感觉传入障碍，但在星形胶质细胞或神经元。总之，显示MAPK信号的小胶质细胞似乎有助于在中央听觉区的适应性反应，直接或间接受到感觉传入阻滞。此外，小胶质细胞在时间和空间上参与VCN内的突触发生。(c)2014 Wiley Periodicals，Inc.
Cochlear ablation triggers cellular and molecular reactions in the adult mammalian central auditory system, leading to complex rearrangements in the cellular networks of the auditory brainstem. The role of microglial cells in these processes is largely unknown. We analyzed morphological and molecular responses as well as cellular affiliations of microglia in the auditory brainstem 1 and 7 days after unilateral sensory deafferentation of the cochlear nucleus. In the ventral cochlear nucleus (VCN), morphological changes of microglial cells were evident following cochlear ablation. Microglial activation preceded astroglial hypertrophy in VCN and lateral superior olive (LSO). During axonal degeneration in VCN early after cochlear ablation, p-ERK1/2- and p-p38-immunoreactive microglia displayed a hypertrophied phenotype, with processes partially surrounding glutamatergic but not GABAergic synapses. During the peak of VCN reinnervation 1 week after cochlear ablation, the number of microglial cells increased massively. Microglia now displayed dense ramifications juxtaposed to Gap43-immunoreactive axons and their terminals. Moreover, we identified lesion-dependent changes in the populations of microglia and astrocytes in LSO and inferior colliculus. By covisualizing cytological markers such as NeuN, GFAP, CD11b, vGluT-1, GAD-65, and Gap43 with the prominent MAP kinases ERK1/2 and p38, we show that MAPK signaling is affected by sensory deafferentation in microglia but not in astroglia or in neurons. In conclusion, microglia displaying MAPK signaling appear to contribute to an adaptive response in central auditory regions that was directly or indirectly affected by sensory deafferentation. Moreover, microglial cells are temporally and spatially in place to participate in synaptogenesis inside VCN. (c) 2014 Wiley Periodicals, Inc.