D-Cycloserine improves sociability in the BTBR T+ Itpr3tf/J mouse model of autism spectrum disorders with altered Ras/Raf/ERK1/2 signaling.
D-Cycloserine improves sociability in the BTBR T+ Itpr3tf/J mouse model of autism spectrum disorders with altered Ras/Raf/ERK1/2 signaling.
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DOI：
10.1016/j.brainresbull.2013.05.003
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发表时间：
2013-07
影响因子：
3.8
通讯作者：
Deutsch SI
中科院分区：
文献类型：
--
作者：
Burket JA;Benson AD;Tang AH;Deutsch SI
遗传近交系BTBR T+Itpr3tf/J(BTBR)小鼠是一种建议的自闭症谱系障碍(ASDS)模型。类似于几种综合征形式的自闭症，mTOR活性在这种小鼠品系中可能由于RAS信号的增加而增强。最近，针对NMDA受体的D-环丝氨酸，一种针对NMDA受体的部分甘氨酸B位点激动剂，被证明可以改善Balb/c小鼠品系的社交能力，这是另一种被提出的ASD遗传近亲繁殖模型。NMDA受体激活是mTOR信号活性的重要调节因子。鉴于d-环丝氨酸能够改善Balb/c小鼠品系的社交能力，以及NMDA受体在mTOR信号中的调节作用，我们想知道d-环丝氨酸是否会改善BTBR小鼠品系受损的社交能力。D-环丝氨酸(320 mg/kg，ip)改善了在BTBR品系中与ICR刺激鼠进行社交互动时出现的标准社交范式中的社交测量和自发梳理；然而，在瑞士Webster比较品系中观察到了类似的效果，这引发了对其品系选择性的质疑。重要的是，d-环丝氨酸对社交能力和刻板印象的影响与治疗自闭症的理想药物一致；具体地说，理想的药物不会以恶化刻板印象行为为代价来改善社交能力，反之亦然。
The genetically inbred BTBR T+ Itpr3tf/J (BTBR) mouse is a proposed model of autism spectrum disorders (ASDs). Similar to several syndromic forms of ASDs, mTOR activity may be enhanced in this mouse strain as a result of increased Ras signaling. Recently, d-cycloserine, a partial glycineB site agonist that targets the NMDA receptor, was shown to improve the sociability of the Balb/c mouse strain, another proposed genetically inbred model of ASDs. NMDA receptor activation is an important regulator of mTOR signaling activity. Given the ability of d-cycloserine to improve the sociability of the Balb/c mouse strain and the regulatory role of the NMDA receptor in mTOR signaling, we wondered if d-cycloserine would improve the impaired sociability of the BTBR mouse strain. d-Cycloserine (320 mg/kg, ip) improved measures of sociability in a standard sociability paradigm and spontaneous grooming that emerged during social interaction with an ICR stimulus mouse in the BTBR strain; however, similar effects were observed in the Swiss Webster comparator strain, raising questions about their strain-selectivity. Importantly, the profile of d-cycloserine's effects on both measures of sociability and stereotypies is consistent with that of a desired medication for ASDs; specifically, a desired medication would not improve sociability at the expense of worsening stereotypic behaviors or vice versa.
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