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首页> 外文期刊>BMC Neuroscience >Transient change in GABA A receptor subunit mRNA expression in Lurcher cerebellar nuclei during Purkinje cell degeneration
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Transient change in GABA A receptor subunit mRNA expression in Lurcher cerebellar nuclei during Purkinje cell degeneration

机译：浦肯野细胞变性期间小L核中GABA A受体亚基mRNA表达的瞬时变化

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Background Lurcher mice suffer from a complete Purkinje cell (PC) loss in the first four postnatal weeks. Parallel to this degeneration, GABAergic synapses in the deep cerebellar nuclei (DCN), the major recipient of the inhibitory PC projection, increase synaptic conductance. Here, we further investigated this phenomenon, using real-time RT-PCR to assess GABAA receptor subunit gene expression during PC degeneration. Results We observed a specific reduction in γ2 subunit gene expression, while α1–5, β1–2, γ1,3 and δ subunits were unaffected. We made two further specific findings. First, the difference in gene expression was shown in tissue from DCN only. Neither the hippocampus nor coronal sections through the forebrain showed such effects. Furthermore, the involvement of different levels of corticosterone, a possible humeral trigger for differences in gene expression, could be excluded. Second, like the known potentiation of GABAergic synapses, the γ2 down-regulation was present only after the onset of degeneration at p14. The difference in γ2 mRNA expression, however, appeared transient, since it was no longer detectable in adult Lurcher mice. Conclusion In conclusion, the down-regulation of γ2 subunits may be related to differences in synaptic efficacy and, as such, may reflect the initial phase of adaptive responses of DCN tissue to massive GABAergic deafferentation. Its transient course, however, does not support the idea that modulations in GABAergic transmission are at the basis of the well-known DCN-based functional benefit of Lurcher mice present throughout their life.
机译：背景Lurcher小鼠在出生后的前四周遭受了完全的Purkinje细胞（PC）损失。与此平行的是，抑制性PC投射的主要接受者小脑深核（DCN）中的GABA能突触增加了突触传导。在这里，我们通过实时RT-PCR评估PC变性期间GABA A 受体亚基基因表达，进一步研究了这种现象。结果我们观察到了γ2亚基基因表达的特异性降低，而α1–5，β1–2，γ1,3和δ亚基未受影响。我们做出了另外两个具体发现。首先，仅在DCN的组织中显示了基因表达的差异。通过前脑的海马和冠状切片均未显示出这种作用。此外，可以排除皮质酮的不同水平的参与，这可能是基因表达差异的可能的肱骨触发。其次，就像已知的GABA能突触增强一样，仅在p14变性开始后才存在γ2下调。然而，由于不再在成年Lurcher小鼠中检测到，因此γ2mRNA表达的差异似乎是短暂的。结论总之，γ2亚基的下调可能与突触效力的差异有关，因此，这可能反映了DCN组织对大量GABA能脱除咖啡因的适应性反应的初始阶段。然而，它的短暂过程并不支持这样的想法，即GABA能传递的调节是Lurcher小鼠一生中存在的众所周知的基于DCN的功能优势的基础。

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