Analysis of VMAT2 binding after methamphetamine or MPTP treatment: Disparity between homogenates and vesicle preparations
Analysis of VMAT2 binding after methamphetamine or MPTP treatment: Disparity between homogenates and vesicle preparations
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DOI：
10.1046/j.1471-4159.2000.0742217.x
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发表时间：
2000-05-01
影响因子：
4.7
通讯作者：
Sonsalla, PK
中科院分区：
文献类型：
--
作者：
Hogan, KA;Staal, RGW;Sonsalla, PK
[H-3]二氢丁苯那嗪（[H-3]DTBZ）是囊泡单胺转运体（VMAT 2）的特异性配体，已被用于表征实验动物和人类单胺能神经末梢的完整性。本研究的目的是比较与其他神经化学标记的多巴胺（DA）神经末梢的神经毒性剂量的甲基苯丙胺（METH）或MPTP治疗的小鼠的VMAT 2结合的损失。在暴露于神经毒素后1天和6天，在纹状体匀浆中观察到DA含量、酪氨酸羟化酶活性和[H-3]甲氧羰基-3-（4-氟苯基）托烷与DA转运蛋白结合的显著降低（大于或等于70%）。令人惊讶的是，在暴露后1天，未观察到匀浆中[H-3]DTBZ结合的显著损失，尽管6天后显著损失（约50%）明显。然而，在分离的囊泡制剂中，[H-3]DTBZ结合和活性[H-3]DA摄取在1天时显著降低（>70%）。这些观察结果表明，囊泡功能在暴露于神经毒性损伤后的早期时间点受损。此外，[H-3]DTBZ结合匀浆中的变化可能不是突触囊泡早期损伤的敏感指标，尽管匀浆结合可靠地识别VMAT 2在以后的时间损失。
[H-3]Dihydrotetrabenazine ([H-3]DTBZ), a specific ligand for the vesicular monoamine transporter (VMAT2), has been used to characterize the integrity of monoaminergic nerve terminals in experimental animals and humans. The purpose of the present studies was to compare the loss of VMAT2 binding with the loss of other neurochemical markers of the dopamine (DA) nerve terminals in mice treated with neurotoxic doses of methamphetamine (METH) or MPTP. Profound decreases (greater than or equal to 70%) in DA content, tyrosine hydroxylase activity, and [H-3]carbomethoxy-3-(4-fluorophenyl)tropane binding to the DA transporter were observed in striatal homogenates at both 1 and 6 days after exposure to the neurotoxins. It is surprising that no significant loss of [H-3]DTBZ binding in the homogenates was observed at 1 day after exposure, although a significant loss (-50%) was apparent 6 days later. However, in isolated vesicle preparations, [H-3]DTBZ binding and active [H-3]DA uptake were markedly reduced (>70%) at 1 day. These observations indicate that vesicle function is compromised at an early time point after exposure to neurotoxic insult. Furthermore, the changes in [H-3]DTBZ binding in homogenates may not be a sensitive indicator of early damage to synaptic vesicles, although homogenate binding reliably identifies a loss of VMAT2 at later times.