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首页> 外文期刊>The European Journal of Neuroscience >Long-term depression of cortico-striatal synaptic transmission by DHPG depends on endocannabinoid release and nitric oxide synthesis.
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Long-term depression of cortico-striatal synaptic transmission by DHPG depends on endocannabinoid release and nitric oxide synthesis.

机译:DHPG对皮质-纹状体突触传递的长期抑制取决于内源性大麻素的释放和一氧化氮的合成。

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摘要

In models of early stage Parkinson's disease (PD), motor deficits are accompanied by excessive activation of striatal glutamate receptors. Metabotropic glutamate group I receptors (mGluR I) play an important but not well-understood role in PD progression. In mouse brain slices, bath application of the mGluR I agonist (RS)-DHPG (3,5-dihydroxyphenylglycine, 100 microm for 20 min) caused a long-term depression of corticostriatal transmission (LTD(DHPG)), which was reversed by three mGluR I antagonists: LY 367385, CPCCOEt and MPEP. LTD(DHPG) required nitric oxide (NO) synthesis as it was blocked by the broad-spectrum NO synthase (NOS) inhibitor Nomega-nitro-l-arginine (NL-Arg) and impaired under blockade of neuronal NOS and in endothelial NOS-deficient mice. Release of endocannabinoids (eCB) was critically involved in this form of striatal plasticity givem that the CB1 receptor antagonist AM251 prevented LTD(DHPG), while the CB1 agonist ACEA elicited LTD. The NO synthesis necessary for LTD(DHPG) induction occurred downstream of CB1 activation as ACEA-evoked LTD was also abolished by NL-Arg. These findings are relevant for the pathophysiology of PD, as they link the overactivation of group I mGluRs and striatal NO production.
机译:在早期帕金森氏病(PD)模型中,运动功能障碍伴有纹状体谷氨酸受体的过度活化。 I型代谢型谷氨酸受体(mGluR I)在PD进展中起着重要但未被充分理解的作用。在小鼠脑切片中,洗澡时使用mGluR I激动剂(RS)-DHPG(3,5-二羟基苯基甘氨酸,100微米,持续20分钟)会导致皮质骨皮质传递的长期抑制(LTD(DHPG)),可通过逆转三种mGluR I拮抗剂:LY 367385,CPCCOEt和MPEP。 LTD(DHPG)需要一氧化氮(NO)的合成,因为它被广谱NO合酶(NOS)抑制剂Nomega-硝基-1-精氨酸(NL-Arg)所阻断,并在神经元NOS和内皮NOS-的阻滞下受损缺陷小鼠。内源性大麻素(eCB)的释放与这种形式的纹状体可塑性物质至关重要,CB1受体拮抗剂AM251阻止LTD(DHPG),而CB1激动剂ACEA引起LTD。 LTD(DHPG)诱导所需的NO合成发生在CB1激活的下游,因为ACE-诱发的LTD也被NL-Arg废除了。这些发现与PD的病理生理学有关,因为它们将I类mGluRs的过度活化与纹状体NO的产生联系起来。

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