mGluR5-antagonist mediated reversal of elevated stereotyped, repetitive behaviors in the VPA model of autism.
mGluR5-antagonist mediated reversal of elevated stereotyped, repetitive behaviors in the VPA model of autism.
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DOI：
10.1371/journal.pone.0026077
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Siegel SJ
中科院分区：
文献类型：
--
作者：
Mehta MV;Gandal MJ;Siegel SJ
自闭症谱系障碍(ASD)是一种高度致残性的发育障碍，人口患病率为1-3%。尽管有很强的遗传病因，但目前还没有针对ASD核心症状的治疗选择。新的证据表明，谷氨酸能信号转导功能障碍，特别是通过代谢性谷氨酸受体5(MGluR5)受体，可能导致表型缺陷，并可能成为药物干预的合适靶点。本研究评估了mGluR5受体拮抗剂2-甲基-6-苯乙基-吡啶(MPEP)对丙戊酸(VPA)自闭症小鼠重复和焦虑样行为的治疗潜力。小鼠在出生前13天暴露于VPA中，并在成年后评估重复的自我打扮和大理石埋藏行为。在开阔场地测量焦虑样行为和运动活动。暴露于VPA的小鼠表现出更多的重复和焦虑样行为，这与之前发表的结果一致。在大理石埋藏和自我梳理试验中，MPEP显著减少了VPA处理的小鼠的重复行为，但对运动活动没有影响。这些结果与新兴的临床前文献一致，即mGluR5拮抗剂可能对自闭症的核心症状具有治疗效果。
Autism spectrum disorders (ASD) are highly disabling developmental disorders with a population prevalence of 1–3%. Despite a strong genetic etiology, there are no current therapeutic options that target the core symptoms of ASD. Emerging evidence suggests that dysfunction of glutamatergic signaling, in particular through metabotropic glutamate receptor 5 (mGluR5) receptors, may contribute to phenotypic deficits and may be appropriate targets for pharmacologic intervention. This study assessed the therapeutic potential of 2-methyl-6-phenylethyl-pyrididine (MPEP), an mGluR5-receptor antagonist, on repetitive and anxiety-like behaviors in the valproic acid (VPA) mouse model of autism. Mice were exposed prenatally on day E13 to VPA and assessed for repetitive self-grooming and marble burying behaviors as adults. Anxiety-like behavior and locomotor activity were measured in an open-field. VPA-exposed mice displayed increased repetitive and anxiety-like behaviors, consistent with previously published results. Across both marble burying and self-grooming assays, MPEP significantly reduced repetitive behaviors in VPA-treated mice, but had no effect on locomotor activity. These results are consistent with emerging preclinical literature that mGluR5-antagonists may have therapeutic efficacy for core symptoms of autism.
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影响因子：
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作者：
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Ritz, Louise
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Hensch, Takao K.
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通讯作者：
Jongens, TA
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作者：
Brodkin, J;Busse, C;Varney, MA
通讯作者：
Varney, MA