Parrella Edoardo, Del Gallo Federico, Porrini Vanessa, Gussago Cristina, Benarese Marina, Fabene Paolo Francesco, Pizzi Marina
Division of Pharmacology, Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy.
Section of Anatomy and Histology, Department of Neurosciences, Biomedicine and Movement Sciences, School of Medicine, University of Verona, Verona, Italy.
Front Behav Neurosci. 2022 Mar 11;16:831664. doi: 10.3389/fnbeh.2022.831664. eCollection 2022.
Non-motor symptoms are frequently observed in Parkinson's disease (PD) and precede the onset of motor deficits by years. Among them, neuropsychiatric symptoms, including anxiety, depression, and apathy, are increasingly considered as a major challenge for patients with PD and their caregivers. We recently reported that mice lacking the nuclear factor-κB (NF-κB)/c-Rel protein (c-rel mice) develop an age-dependent PD-like pathology and phenotype characterized by the onset of non-motor symptoms, including constipation and hyposmia, starting at 2 months of age, and motor deficits at 18 months. To assess whether c-rel mice also suffer from neuropsychiatric symptoms, in this study we tested different cohorts of wild-type (wt) and c-rel mice at 3, 6, 12, and 18-20 months with different behavioral tests. Mice lacking c-Rel displayed anxiety and depressive-like behavior starting in the premotor phase at 12 months, as indicated by the analysis with the open field (OF) test and the forced swim test with water wheel (FST), respectively. A deficit in the goal-oriented nesting building test was detected at 18-20 months, suggesting apathetic behavior. Taken together, these results indicate that c-rel mice recapitulate the onset and the progression of PD-related neuropsychiatric symptoms. Therefore, this animal model may represent a valuable tool to study the prodromal stage of PD and for testing new therapeutic strategies to alleviate neuropsychiatric symptoms.
帕金森病（PD）患者常出现非运动症状，且早于运动功能障碍数年出现。其中，包括焦虑、抑郁和冷漠在内的神经精神症状，日益被视为PD患者及其照料者面临的一项重大挑战。我们最近报告称，缺乏核因子-κB（NF-κB）/c-Rel蛋白的小鼠（c-rel小鼠）会出现年龄依赖性的PD样病理和表型，其特征为从2月龄开始出现包括便秘和嗅觉减退在内的非运动症状，18月龄时出现运动功能障碍。为评估c-rel小鼠是否也存在神经精神症状，在本研究中，我们在3、6、12和18 - 20月龄时，使用不同的行为测试对不同组别的野生型（wt）和c-rel小鼠进行了检测。分别通过旷场（OF）试验和带水轮的强迫游泳试验（FST）分析表明，缺乏c-Rel的小鼠在12月龄的运动前期就开始表现出焦虑和抑郁样行为。在18 - 20月龄时，检测到目标导向筑巢试验存在缺陷，提示有冷漠行为。综上所述，这些结果表明c-rel小鼠重现了PD相关神经精神症状的发生和进展。因此，这种动物模型可能是研究PD前驱期以及测试缓解神经精神症状新治疗策略的宝贵工具。
