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首页> 外文期刊>The European Journal of Neuroscience >Inflammation alters AMPA-stimulated calcium responses in dorsal striatal D2 but not D1 spiny projection neurons
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Inflammation alters AMPA-stimulated calcium responses in dorsal striatal D2 but not D1 spiny projection neurons

机译：炎症改变了淋巴纹纹状体D2中的AMPA刺激的钙应答，但不是D1多刺的投影神经元

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Neuroinflammation precedes neuronal loss in striatal neurodegenerative diseases and can be exacerbated by the release of proinflammatory molecules by microglia. These molecules can affect trafficking of AMPARs. The preferential trafficking of calcium-permeable versus impermeable AMPARs can result in disruptions of [Ca2+]i and alter cellular functions. In striatal neurodegenerative diseases, changes in [Ca2+]i and L-type voltage-gated calcium channels (VGCCs) have been reported. Therefore, this study sought to determine whether a proinflammatory environment alters AMPA-stimulated [Ca2+]i through calcium-permeable AMPARs and/or L-type VGCCs in dopamine-2- and dopamine-1-expressing striatal spiny projection neurons (D2 and D1 SPNs) in the dorsal striatum. Mice expressing the calcium indicator protein, GCaMP in D2 or D1 SPNs, were utilized for calcium imaging. Microglial activation was assessed by morphology analyses. To induce inflammation, acute mouse striatal slices were incubated with lipopolysaccharide (LPS). Here we report that LPS treatment potentiated AMPA responses only in D2 SPNs. When a nonspecific VGCC blocker was included, we observed a decrease of AMPA-stimulated calcium fluorescence in D2 but not D1 SPNs. The remaining agonist-induced [Ca2+]i was mediated by calcium-permeable AMPARs because the responses were completely blocked by a selective calcium-permeable AMPAR antagonist. We used isradipine, the highly selective L-type VGCC antagonist to determine the role of L-type VGCCs in SPNs treated with LPS. Isradipine decreased AMPA-stimulated responses selectively in D2 SPNs after LPS treatment. Our findings suggest that dorsal striatal D2 SPNs are specifically targeted in proinflammatory conditions and that L-type VGCCs and calcium-permeable AMPARs are important mediators of this effect.
机译：神经引发在纹状体神经变性疾病中的神经元损失之前，可以通过微胶质细胞释放促炎分子来加剧。这些分子可以影响贩运安培。钙渗透性易渗透性的安培的优惠贩运可能导致[CA2 +] I的破坏和改变蜂窝功能。在纹状体神经变性疾病中，已经报道了[Ca2 +] I和L型电压门控钙通道（VGCC）的变化。因此，该研究寻求确定促炎环境是否通过多巴胺-2-和多巴胺-1-表达纹纹纹斑节突出神经元（D2和D1 SPNS）在背体纹状体中。表达钙指示剂蛋白质，D2或D1 SPN中的小鼠用于钙成像。通过形态学分析评估微胶质活化。为了诱导炎症，将急性小鼠纹状体切片与脂多糖（LPS）一起温育。在这里，我们报告称LPS处理仅在D2 SPN中具有额度的AMPA响应。当包括非特异性VGCC阻滞剂时，我们观察到D2中的AMPA刺激的钙荧光降低但不是D1 SPN。剩余的激动剂诱导的[Ca2 +] I通过钙渗透性作用的药物介导，因为通过选择性钙可渗透的AMPAR拮抗剂完全阻断反应。我们使用了IsRadipine，高选择性L型VGCC拮抗剂，以确定L型VGCCs在用LPS处理的SPN中的作用。在LPS处理后，IsRadipine在D2 SPN中选择性地减少了AMPA刺激的反应。我们的研究结果表明，背部纹状体D2 SPN专门针对促炎症条件，L型VGCC和钙渗透的药物是这种效果的重要介质。

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