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首页> 外文期刊>Brain research >Heterotrimeric G protein activation rapidly inhibits outgrowth of optic axons from adult and embryonic mouse, and goldfish retinal explants.
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Heterotrimeric G protein activation rapidly inhibits outgrowth of optic axons from adult and embryonic mouse, and goldfish retinal explants.

机译：异源三聚体G蛋白的活化迅速抑制成年和胚胎小鼠以及金鱼视网膜外植体视轴突的生长。

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Axons in the adult mammalian CNS normally do not regenerate following axotomy even though they retain the capacity for growth under certain experimental conditions. Although this implies that the regeneration of adult axons is under regulative control, very little is known about the signaling pathways "responsible" for this regulation. This study examines the possibility that a G protein signaling system exists in adult mouse optic fibers and that it functions to regulate axonal outgrowth. To induce the growth of optic fibers, retinas from adult mouse were placed in organotypic culture under serum free conditions and allowed to regenerate onto a laminin substrate. Heterotrimeric G proteins were stimulated by adding mastoparan (MST) to the medium while monitoring growing fibers with time lapse microscopy. Mastoparan treatment produced rapid growth cone collapse and axonal retraction which persisted while MST was present. Prior addition of pertussis toxin (PTX), which irreversibly inactivates the G proteins, G(o) and G (i),completely blocked the effect of MST, confirming that MST was acting through the PTX sensitive G proteins. Selective activation of G proteins in the growth cone by local application of MST with a micropipet was equally effective. For comparison, equivalent experiments were performed on embryonic day 15 retinal explants and on retinal explants from adult goldfish, which normally regenerate in vivo. MST similarly inhibited these axons and this effect was blocked by PTX. However, embryonic fibers were less reliably affected compared to goldfish or adult mouse, suggesting a developmentally regulated sensitivity. The presence of G-proteins in the mouse axons was further tested immunohistochemically using antibodies against G(o)/G(i). Positive staining was detected in the growth cones and shaft of adult and embryonic mouse optic fibers. These findings demonstrate that G protein activation inhibits axonal outgrowth and suggest that there may be a G protein signaling pathway that normally regulates this outgrowth. However, since this pathway appears to exist in both axons that can regenerate and those that normally do not, the presence of PTX-sensitive G proteins alone cannot account for regenerative failure. Regenerative failure may instead be explained as the selective or increased activation of this pathway in the adult mammalian CNS.
机译：即使在某些实验条件下，成年哺乳动物中枢神经系统中的轴突通常不会再生，即使它们在某些实验条件下仍能生长。尽管这意味着成年轴突的再生处于调节性控制之下，但对于这种调节“负责”的信号传导途径知之甚少。这项研究检查了成年小鼠视神经纤维中存在G蛋白信号传导系统以及其调节轴突生长的可能性。为了诱导光纤的生长，将成年小鼠的视网膜在无血清条件下置于器官型培养物中，并使其再生至层粘连蛋白底物上。异三聚体G蛋白可通过向培养基中添加马索帕兰（MST）来刺激，同时通过延时显微镜观察生长中的纤维。 Mastoparan治疗产生快速的生长锥塌陷和轴突收缩，当存在MST时持续存在。事先添加不可逆地失活G蛋白G（o）和G（i）的百日咳毒素（PTX）完全阻断了MST的作用，证实MST通过PTX敏感的G蛋白起作用。通过用微量移液管局部应用MST选择性激活生长锥中的G蛋白同样有效。为了比较，在胚胎第15天视网膜外植体和成年金鱼的视网膜外植体上进行了等效的实验，它们通常在体内再生。 MST同样抑制了这些轴突，并且该作用被PTX阻断。但是，与金鱼或成年小鼠相比，胚胎纤维受到的影响较小，表明其敏感性受到发育调节。使用抗G（o）/ G（i）抗体通过免疫组织化学进一步测试了小鼠轴突中G蛋白的存在。在成年和胚胎小鼠光纤的生长锥和轴中检测到阳性染色。这些发现表明，G蛋白激活抑制轴突生长，并暗示可能存在正常调节该生长的G蛋白信号传导途径。但是，由于该途径似乎存在于可再生的轴突和通常不再生的轴突中，因此仅PTX敏感的G蛋白的存在不能解释再生失败。可以将再生失败解释为成年哺乳动物中枢神经系统中该途径的选择性激活或增强激活。

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