Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Vic., Australia.
Department of Anatomy and Neuroscience, University of Melbourne, Parkville, Vic., Australia.
Neurogastroenterol Motil. 2020 Mar;32(3):e13755. doi: 10.1111/nmo.13755. Epub 2019 Nov 10.
Chronic stress exacerbates motor deficits and increases dopaminergic cell loss in several rodent models of Parkinson's disease (PD). However, little is known about effects of stress on gastrointestinal (GI) dysfunction, a common non-motor symptom of PD. We aimed to determine whether chronic stress exacerbates GI dysfunction in the A53T mouse model of PD and whether this relates to changes in α-synuclein distribution.
Chronic isolation stress was induced by single-housing WT and homozygote A53T mice between 5 and 15 months of age. GI and motor function were compared with mice that had been group-housed.
Chronic isolation stress increased plasma corticosterone and exacerbated deficits in colonic propulsion and whole-gut transit in A53T mice and also increased motor deficits. However, our results indicated that the novel environment-induced defecation response, a common method used to evaluate colorectal function, was not a useful test to measure exacerbation of GI dysfunction, most likely because of the reported reduced level of anxiety in A53T mice. A53T mice had lower corticosterone levels than WT mice under both housing conditions, but single-housing increased levels for both genotypes. Enteric neuropathy was observed in aging A53T mice and A53T mice had a greater accumulation of alpha-synuclein (αsyn) in myenteric ganglia under both housing conditions.
CONCLUSIONS & INFERENCES: Chronic isolation stress exacerbates PD-associated GI dysfunction, in addition to increasing motor deficits. However, these changes in GI symptoms are not directly related to corticosterone levels, worsened enteric neuropathy, or enteric αsyn accumulation.
慢性应激会加剧几种帕金森病（PD）啮齿动物模型的运动缺陷，并增加多巴胺能细胞的丢失。然而，对于应激对胃肠道（GI）功能障碍的影响，即 PD 的一种常见非运动症状，人们知之甚少。我们旨在确定慢性应激是否会加剧 A53T PD 小鼠模型的 GI 功能障碍，以及这种情况是否与α-突触核蛋白分布的变化有关。
将 WT 和纯合 A53T 小鼠在 5 至 15 个月大时进行单笼饲养，以诱导慢性隔离应激。将 GI 和运动功能与群养的小鼠进行比较。
慢性隔离应激增加了 A53T 小鼠的血浆皮质酮水平，并加剧了其结肠推进和全肠转运的缺陷，同时也增加了运动缺陷。然而，我们的结果表明，新型环境诱发的排便反应（一种常用于评估结直肠功能的常用方法）并不是衡量 GI 功能障碍加重的有用测试，这很可能是因为 A53T 小鼠报告的焦虑水平降低。在两种饲养条件下，A53T 小鼠的皮质酮水平均低于 WT 小鼠，但单笼饲养会增加两种基因型的皮质酮水平。在衰老的 A53T 小鼠中观察到肠神经病，并且在两种饲养条件下，A53T 小鼠的肌间神经节中α-突触核蛋白（αsyn）的积累更多。
慢性隔离应激除了增加运动缺陷外，还会加剧与 PD 相关的 GI 功能障碍。然而，这些 GI 症状的变化与皮质酮水平、恶化的肠神经病或肠内 αsyn 积累没有直接关系。
