Glial-derived adenosine modulates spinal motor networks in mice.
Glial-derived adenosine modulates spinal motor networks in mice.
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胶质细胞来源的腺苷调节小鼠的脊髓运动网络。
DOI：
10.1152/jn.00513.2011
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发表时间：
2012
影响因子：
2.5
通讯作者：
Witts EC
中科院分区：
文献类型：
--
作者：
Witts EC
嘌呤能受体的激活调节控制节律运动行为的中枢模式发生器，包括啮齿类动物的呼吸和青蛙蝌蚪的游泳。本研究旨在确定嘌呤能信号传导是否也调节哺乳动物运动中枢模式发生器。这是通过使用从新生小鼠获得的分离脊髓制剂进行研究的，其中可以通过药理学诱导运动相关活动。 ATP 或腺苷的应用导致腹根记录的运动活动频率减少。当腺苷受体拮抗剂茶碱和核酸外切酶抑制剂 ARL67156 存在时，ATP 没有作用，这表明 ATP 应用的作用是由于 ATP 分解为腺苷并随后激活腺苷受体所致。应用茶碱或 A1 特异性拮抗剂环戊基二丙基黄嘌呤（而非 A2A 受体拮抗剂 SCH58261）会导致运动爆发频率增加，表明内源性腺苷在运动网络活动期间激活 A1 受体。此外，茶碱在核酸外切酶抑制剂 ARL67156 或神经胶质毒素甲硫氨酸亚砜亚胺或氟乙酸乙酯存在下没有作用，这表明内源性腺苷源自神经胶质细胞释放的 ATP。最后，腺苷对阻断所有抑制性传播时记录的慢节律活动没有影响，这表明腺苷可能通过调节抑制性传播发挥作用。总之，这些数据强调了内源性嘌呤能神经胶质传递，涉及 A1 受体的激活，作为控制哺乳动物脊髓运动回路产生的活动频率的重要内在调节系统。
The activation of purinergic receptors modulates central pattern generators controlling rhythmic motor behaviors, including respiration in rodents and swimming in frog tadpoles. The present study aimed to determine whether purinergic signaling also modulates the mammalian locomotor central pattern generator. This was investigated by using isolated spinal cord preparations obtained from neonatal mice in which locomotor-related activity can be induced pharmacologically. The application of either ATP or adenosine led to a reduction in the frequency of locomotor activity recorded from ventral roots. ATP had no effect when applied in the presence of both the adenosine receptor antagonist theophylline and the ectonucleotidase inhibitor ARL67156, demonstrating that the effects of ATP application result from the breakdown of ATP to adenosine and subsequent activation of adenosine receptors. The application of theophylline or the A1-specific antagonist cyclopentyl dipropylxanthine, but not the A2A-receptor antagonist SCH58261, caused an increase in locomotor burst frequency, demonstrating that endogenously derived adenosine activates A1receptors during locomotor network activity. Furthermore, theophylline had no effect in the presence of the ectonucleotidase inhibitor ARL67156 or the glial toxins methionine sulfoximine or ethyl fluoracetate, suggesting that endogenous adenosine is derived from ATP, which is released from glia. Finally, adenosine had no effect on slow rhythmic activity recorded upon blockade of all inhibitory transmission, suggesting that adenosine may act via the modulation of inhibitory transmission. Together, these data highlight endogenous purinergic gliotransmission, involving activation of A1receptors, as an important intrinsic modulatory system controlling the frequency of activity generated by spinal locomotor circuitry in mammals.