针对外周体感神经元来改善ASD模型中的触觉相关表型
Lauren L Orefice1, Jacqueline R Mosko1, Danielle T Morency1
1Department of Neurobiology, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA; Howard Hughes Medical Institute, Harvard Medical School, 220 Longwood Avenue, Boston, MA 02115, USA.
Cell
|August 10, 2019
概括
在自闭症谱系障碍 (ASD) 中治疗感官过度反应是具有挑战性的. 这项研究发现,用GABA A受体激动剂向外围机械感应神经元,有效降低了小鼠模型中的触觉过敏和一些与ASD相关的行为.
科学领域:
- 神经科学
- 发育生物学
- 遗传学
背景情况:
- 体感过度反应是自闭症谱系障碍 (ASD) 的常见特征,可能导致核心行为症状.
- 目前对感官过度反应和自闭症的治疗方法仍然有限,强调需要新的治疗方法.
研究的目的:
- 在不同自闭症谱系障碍 (ASD) 鼠标模型中研究体感过度反应的病理生理机制.
- 探索针对外围机械感应神经元作为与自闭症相关的感觉异常和行为治疗策略的潜力.
主要方法:
- 在Shank3和Mecp2突变自闭症小鼠模型中检查了不同的体感神经元病理机制.
- 研究了用局部限制的GABA A受体激动剂对机械感应神经元的急性和慢性治疗的影响.
- 评估行为结果,包括触觉过度反应,类似焦虑的行为,社会障碍,记忆力,运动缺陷和过度理.
主要成果:
- 外围机械感应神经元的发育基因损失 (Shank3,Mecp2) 导致特定区域的大脑异常,并导致与自闭症相关的行为.
- 在六种不同的自闭症小鼠模型中,用GABA A受体激活剂的急性治疗显著降低了触觉过度反应.
- 慢性治疗改善了Mecp2和Shank3突变小鼠的某些身体和行为方面,尽管并非所有缺陷都得到改善.
结论:
- 周围机械感应神经元功能障碍在ASD小鼠模型中的触觉异常和相关行为中起作用.
- 用GABA A受体激动剂向外围机械感应神经元,为ASD的触觉过度反应提供了一个有希望的治疗途径.
- 这种方法可能提供一种解决特定自闭症相关行为的策略,尽管需要进一步研究更广泛的应用.
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