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脊髓损伤前后 Thy1-GFP-M 小鼠的独特感觉和运动行为。

Unique Sensory and Motor Behavior in Thy1-GFP-M Mice before and after Spinal Cord Injury.

机构信息

1 Neuroscience Graduate Program, The Ohio State University , Columbus, Ohio.

2 School of Health and Rehabilitation Sciences, The Ohio State University , Columbus, Ohio.

出版信息

J Neurotrauma. 2018 Sep 15;35(18):2167-2182. doi: 10.1089/neu.2017.5395. Epub 2018 Jun 5.

Abstract

Sensorimotor recovery after spinal cord injury (SCI) is of utmost importance to injured individuals and will rely on improved understanding of SCI pathology and recovery. Novel transgenic mouse lines facilitate discovery, but must be understood to be effective. The purpose of this study was to characterize the sensory and motor behavior of a common transgenic mouse line (Thy1-GFP-M) before and after SCI. Thy1-GFP-M positive (TG+) mice and their transgene negative littermates (TG-) were acquired from two sources (in-house colony, n = 32, Jackson Laboratories, n = 4). C57BL/6J wild-type (WT) mice (Jackson Laboratories, n = 10) were strain controls. Moderate-severe T9 contusion (SCI) or transection (TX) occurred in TG+ (SCI, n = 25, TX, n = 5), TG- (SCI, n = 5), and WT (SCI, n = 10) mice. To determine responsiveness to rehabilitation, a cohort of TG+ mice with SCI (n = 4) had flat treadmill (TM) training 42-49 days post-injury (dpi). To characterize recovery, we performed Basso Mouse Scale, Grid Walk, von Frey Hair, and Plantar Heat Testing before and out to day 42 post-SCI. Open field locomotion was significantly better in the Thy1 SCI groups (TG+ and TG-) compared with WT by 7 dpi (p < 0.01) and was maintained through 42 dpi (p < 0.01). These unexpected locomotor gains were not apparent during grid walking, indicating severe impairment of precise motor control. Thy1 derived mice were hypersensitive to mechanical stimuli at baseline (p < 0.05). After SCI, mechanical hyposensitivity emerged in Thy1 derived groups (p < 0.001), while thermal hyperalgesia occurred in all groups (p < 0.001). Importantly, consistent findings across TG+ and TG- groups suggest that the effects are mediated by the genetic background rather than transgene manipulation itself. Surprisingly, TM training restored mechanical and thermal sensation to baseline levels in TG+ mice with SCI. This behavioral profile and responsiveness to chronic training will be important to consider when choosing models to study the mechanisms underlying sensorimotor recovery after SCI.

摘要

脊髓损伤 (SCI) 后的感觉运动恢复对受伤个体至关重要,这将依赖于对 SCI 病理和恢复的深入理解。新型转基因小鼠品系有助于发现,但必须了解其有效性。本研究的目的是在 SCI 前后描述一种常见转基因小鼠品系(Thy1-GFP-M)的感觉和运动行为。从两个来源获得 Thy1-GFP-M 阳性 (TG+) 小鼠及其转基因阴性同窝仔鼠 (TG-)(内部品系,n = 32,杰克逊实验室,n = 4)。C57BL/6J 野生型 (WT) 小鼠(杰克逊实验室,n = 10)为品系对照。中度严重的 T9 挫伤(SCI)或横断(TX)发生在 TG+(SCI,n = 25,TX,n = 5)、TG-(SCI,n = 5)和 WT(SCI,n = 10)小鼠中。为了确定对康复的反应性,一组 SCI 后的 TG+ 小鼠(n = 4)在损伤后 42-49 天进行了平板跑步机 (TM) 训练。为了描述恢复情况,我们在 SCI 前和 SCI 后 42 天进行了 Basso 小鼠量表、网格行走、von Frey 毛发和足底热测试。与 WT 相比,7dpi 时 Thy1 SCI 组(TG+ 和 TG-)的旷场运动明显更好(p < 0.01),并持续到 42dpi(p < 0.01)。网格行走时这些意外的运动增益并不明显,表明精确运动控制严重受损。Thy1 衍生的小鼠在基线时对机械刺激敏感(p < 0.05)。SCI 后,Thy1 衍生组出现机械感觉迟钝(p < 0.001),而所有组均出现热痛觉过敏(p < 0.001)。重要的是,TG+ 和 TG- 组的一致发现表明,这些影响是由遗传背景介导的,而不是由转基因操作本身介导的。令人惊讶的是,TM 训练使 SCI 后 TG+ 小鼠的机械和热感觉恢复到基线水平。这种行为特征和对慢性训练的反应性在选择研究 SCI 后感觉运动恢复机制的模型时将非常重要。

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