Longitudinal magnetic resonance imaging reveals striatal hypertrophy in a rat model of long-term stimulant treatment.
Longitudinal magnetic resonance imaging reveals striatal hypertrophy in a rat model of long-term stimulant treatment.
复制标题
DOI：
10.1038/tp.2016.158
复制
发表时间：
2016-09-06
影响因子：
6.8
通讯作者：
Posner J
中科院分区：
文献类型：
--
作者：
Biezonski D;Shah R;Krivko A;Cha J;Guilfoyle DN;Hrabe J;Gerum S;Xie S;Duan Y;Bansal R;Leventhal BL;Peterson BS;Kellendonk C;Posner J
兴奋剂治疗在减轻与注意力缺陷/多动障碍（ADHD）相关的症状方面非常有效，尽管这种作用的神经生物学基础尚未确定。使用解剖磁共振成像 (MRI) 对 ADHD 儿童进行的研究表明，长期兴奋剂治疗可能通过刺激纹状体肥大来部分改善 ADHD 的症状。然而，这一结论是有限的，因为这些研究要么使用横断面抽样，要么没有评估治疗长度对其相关指标的影响。因此，我们在车辆对照研究设计中使用纵向解剖 MRI，以确认临床相关长期兴奋剂治疗的啮齿动物模型中兴奋剂对纹状体形态的影响的因果关系。 Sprague Dawley 大鼠从出生后第 25 天（PD25，幼年幼鼠）到 PD95（幼年成年鼠）口服赖右苯丙胺（LDX，“Vyvanse”）或赋形剂（每组 12 只），并在 70 天疗程的前一天和后一天进行成像。我们的 LDX 给药方案产生的右旋苯丙胺血液水平与患者记录的水平相当。纹状体体积的纵向分析显示，与媒介物处理的对照相比，LDX 处理的动物显着肥大，并且通过时间点相互作用进行显着的处理。这些发现证实了长期兴奋剂治疗与纹状体肥大之间的因果关系，并支持啮齿动物中纵向 MRI 作为连接临床前和临床研究的转化方法的实用性。使用相同的成像技术在人类和啮齿动物中证明了类似的形态学效应，未来的研究现在可以使用这种啮齿动物模型来确定兴奋剂诱导的纹状体肥大的潜在细胞机制和行为后果。
Stimulant treatment is highly effective in mitigating symptoms associated with attention-deficit/hyperactivity disorder (ADHD), though the neurobiological underpinnings of this effect have not been established. Studies using anatomical magnetic resonance imaging (MRI) in children with ADHD have suggested that long-term stimulant treatment may improve symptoms of ADHD in part by stimulating striatal hypertrophy. This conclusion is limited, however, as these studies have either used cross-sectional sampling or did not assess the impact of treatment length on their dependent measures. We therefore used longitudinal anatomical MRI in a vehicle-controlled study design to confirm causality regarding stimulant effects on striatal morphology in a rodent model of clinically relevant long-term stimulant treatment. Sprague Dawley rats were orally administered either lisdexamfetamine (LDX, ‘Vyvanse') or vehicle (N=12 per group) from postnatal day 25 (PD25, young juvenile) until PD95 (young adult), and imaged one day before and one day after the 70-day course of treatment. Our LDX dosing regimen yielded blood levels of dextroamphetamine comparable to those documented in patients. Longitudinal analysis of striatal volume revealed significant hypertrophy in LDX-treated animals when compared to vehicle-treated controls, with a significant treatment by time point interaction. These findings confirm a causal link between long-term stimulant treatment and striatal hypertrophy, and support utility of longitudinal MRI in rodents as a translational approach for bridging preclinical and clinical research. Having demonstrated comparable morphological effects in both humans and rodents using the same imaging technology, future studies may now use this rodent model to identify the underlying cellular mechanisms and behavioral consequences of stimulant-induced striatal hypertrophy.
登录
查看更多内容
DOI：
10.1073/pnas.0402680101
发表时间：
2004-05-25
影响因子：
11.1
作者：
Gogtay, N;Giedd, JN;Thompson, PM
通讯作者：
Thompson, PM
影响因子：
10.6
作者：
Nigg, JT;Willcutt, EG;Sonuga-Barke, EJS
通讯作者：
Sonuga-Barke, EJS
影响因子：
120.7
作者：
Castellanos, FX;Lee, PP;Rapoport, JL
通讯作者：
Rapoport, JL
影响因子：
7.6
作者：
Cha, Jiook;Fekete, Tomer;Posner, Jonathan
通讯作者：
Posner, Jonathan
影响因子：
5.7
作者：
Burguière E;Monteiro P;Mallet L;Feng G;Graybiel AM
通讯作者：
Graybiel AM