<br>关键期单眼摘除术诱导的网状可塑性取决于 A2a 腺苷受体：星形胶质细胞的可能作用,Experimental Neurology

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关键期单眼摘除术诱导的网状可塑性取决于 A2a 腺苷受体：星形胶质细胞的可能作用
Experimental Neurology ( IF 4.6 ) Pub Date : 2023-04-26 , DOI: 10.1016/j.expneurol.2023.114427
Ana Lucia Tavares-Gomes ₁ , Bruna Teixeira-Silva ₁ , Beatriz Bastos de Moraes Thomasi ₁ , Pablo Trindade ₂ , Sheila Espírito-Santo ₃ , Adriana da Cunha Faria-Melibeu ₁ , Claudio Alberto Serfaty ₁ , Paula Campello-Costa ₁

Affiliation

大鼠的视网膜地形在关键期的出生后前 3 周内发展。先前的研究表明，单眼摘除术以时间依赖性方式导致完整视网膜通路的可塑性。神经胶质纤维酸性蛋白（GFAP）是一种星形胶质细胞标志物，在中枢神经系统损伤后上调。腺苷是一种神经调节剂，通过抑制性 A1 和兴奋性 A2a 受体活性参与视觉系统的发育和可塑性。在此，我们检查了腺苷受体和星形胶质细胞是否对单眼剜除（ME）诱导的可塑性至关重要。我们还研究了 A2a 阻断是否以星形胶质细胞依赖性方式改变视网膜可塑性。将 Lister Hooded 大鼠在出生后第 10 天（PND10）或 PND21 接受单眼摘除术，并在不同的生存时间后进行免疫组化或蛋白质印迹测定。另一组接受含 ELVAX 载体（DMSO）或 SCH58261 （1 μM - 一种 A2a 受体拮抗剂）的软膜下植入，与 ME 在 PND10 处同时植入。存活 72 小时后，评估 GFAP 含量和视网膜可塑性。我们的数据表明，单眼摘除导致对侧上丘中 GFAP 表达的上调。在 PND10 时，在摘除后 72 小时观察到 GFAP 标记略有增加，而在 PND21 时，在存活 1 至 3 周后，在传入神经分离的上丘中检测到 GFAP 增加。腺苷受体的含量在 ME 之后的对侧靶标中也有所不同。在可塑性的早期观察到 A1 受体的短暂增加，而 A2a 受体在后期上调。有趣的是，A2a 受体的局部阻断消除了关键期单眼摘除诱导的 GFAP 增加和视网膜重组。综上所述，这些结果表明星形胶质细胞和 A2a 腺苷受体在皮质下视觉可塑性中存在相关性。

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Retinotectal plasticity induced by monocular enucleation during the critical period is dependent of A2a adenosine receptor: A possible role of astrocytes

The retinotectal topography of rats develops within the first three postnatal weeks during the critical period. Previous studies have shown that monocular enucleation results in plasticity of the intact retinotectal pathway in a time-dependent manner. Glial fibrillary acidic protein (GFAP), an astrocyte marker, is up-regulated after central nervous system injury. Adenosine is a neuromodulator involved in the development and plasticity of the visual system acting through the inhibitory A1 and excitatory A2a receptor activities. Herein, we examined whether adenosine receptors and astrocytes are crucial for monocular enucleation (ME)-induced plasticity. We also investigate whether A2a blockade alters retinotectal plasticity in an astrocyte-dependent manner. Lister Hooded rats were submitted to monocular enucleation at postnatal day 10 (PND10) or PND21 and, after different survival times, were processed for immunohistochemistry or western blotting assays. Another group underwent subpial implantation of ELVAX containing vehicle (DMSO) or SCH58261 (1 μM - an A2a receptor antagonist), simultaneously with ME at PND10. After a 72 h survival, GFAP content and the retinotectal plasticity were evaluated. Our data show that monocular enucleation leads to an upregulation in GFAP expression in the contralateral superior colliculus. At PND10, a slight increase in GFAP labeling was observed at 72 h post-enucleation, while at PND21 GFAP increase was detected in the deafferented superior colliculus after 1 to 3 weeks of survival. The content of adenosine receptors also varies in the contralateral target after ME. A transient increase in A1 receptors is observed in the early periods of plasticity, while A2a receptors are upregulated later. Interestingly, the local blockade of A2a receptors abolished the increase in GFAP and the retinotectal reorganization induced by monocular enucleation during the critical period. Taken together these results suggest a correlation between astrocytes and A2a adenosine receptors in the subcortical visual plasticity.

更新日期：2023-04-26

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