Gene expression of nAChR, SNAP-25 and GAP-43 in skeletal muscles following botulinum toxin A injection: a study in rats
Gene expression of nAChR, SNAP-25 and GAP-43 in skeletal muscles following botulinum toxin A injection: a study in rats
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DOI：
10.1016/j.orthres.2004.08.027
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发表时间：
2005-03-01
影响因子：
2.8
通讯作者：
Smith, BP
中科院分区：
文献类型：
--
作者：
Ma, JJ;Shen, J;Smith, BP
目的：A 型肉毒毒素 (BoNT-A) 用于治疗脑瘫患者的痉挛。 BoNT-A 裂解 SNAP-25 蛋白，阻止乙酰胆碱释放并削弱肌肉。烟碱乙酰胆碱受体 (nAChR) 包括 α、β、δ、γ 和 ε 亚基，以及 GAP-43 蛋白与 BoNT-A 后神经肌肉接头 (NMJ) 的功能恢复相关。为了更好地了解这种功能恢复背后的机制，本研究试图 (1) 记录 BoNT-A 后 NMJ 形态测量的变化，以及 (2) 确定 nAChR 亚基、SNAP-25 和 GAP-43 蛋白的基因表达。 方法：在这项大鼠研究（46 只大鼠）中，将 6 单位/kg 体重的 BoNT-A 注射到腓肠肌中。在注射后一年内评估 NMJ 形态测量和 nAChR 亚基、SNAP-25 和 GAP-43 基因表达的时间过程。结果：NMJ 形态测量：沟道深度在两个月时与对照侧相比减少，并在 BoNT 后 6 个月恢复正常。 nAChR α mRNA和γ mRNA增加3天，7天达到峰值，恢复至对照水平； δ mRNA 在 5 月达到峰值。 Epsilon mRNA 在 7 天时达到峰值。 SNAP-25 mRNA 从 60 天增加到 90 天，6 个月后恢复到对照水平。 GAP-43 mRNA 没有变化。结论：特定的 nAChR 亚基 mRNA 表达上调，然后在两周内恢复正常，先于 NMJ 形态测量的变化。尽管 GAP-43 参与神经萌芽，但 BoNT-A 后 GAP-43 mRNA 没有增加。 SNAP-25 mRNA 的延迟上调可能与肌肉功能恢复有关。 (c) 2004 年骨科研究学会。由爱思唯尔有限公司出版。保留所有权利。
Purpose: Botulinum toxin A (BoNT-A) is used to manage spasticity in cerebral palsy. BoNT-A cleaves SNAP-25 protein, blocking acetylcholine release and weakening the muscle. Nicotinic acetylcholine receptors (nAChR) including alpha, beta, delta, gamma, and epsilon subunits, and GAP-43 protein are associated with functional recovery of neuromuscular junctions (NMJ) following BoNT-A. To better understand the mechanism behind this functional recovery, this study attempted to (1) document changes in NMJ morphometry following BoNT-A, and (2) determine the gene expression of nAChR subunits, SNAP-25, and GAP-43 protein.Methods: In this rat study (46 rats), 6 units/kg body weight of BoNT-A was injected into the gastrocnimus. NMJ morphometry and the time course of gene expression of nAChR subunits, SNAP-25, and GAP-43 were evaluated up to I year post-injection.Results: NMJ morphometry: gutter depth was reduced vs. the control side at two months, and normalizing by 6 months following BoNT. nAChR alpha mRNA and gamma mRNA increased by 3 days, peaked at 7 days and returned to control levels; delta mRNA peaked at Mays. Epsilon mRNA peaked by 7 days. SNAP-25 mRNA increased from 60 to 90 days, returning to control levels by 6 months. GAP-43 mRNA was unchanged.Conclusions: Specific nAChR subunit mRNA expression up-regulates and then returns to normal within two weeks, preceding changes in NMJ morphometry. Although GAP-43 participates in nerve sprouting, no increase of GAP-43 mRNA occurred following BoNT-A. Delayed up-regulation of SNAP-25 mRNA might be associated with muscle functional recovery. (c) 2004 Orthopaedic Research Society. Published by Elsevier Ltd. All rights reserved.