中国神经再生研究(英文版) ›› 2024, Vol. 20 ›› Issue (2): 574-586.doi: 10.4103/NRR.NRR-D-23-00595

• 原著:退行性病与再生 • 上一篇    下一篇

运动和摄入二十二碳六烯酸对帕金森病模型小鼠神经恢复产生叠加效应

  

  • 出版日期:2025-02-15 发布日期:2024-06-18
  • 基金资助:
    加拿大帕金森协会的资助项目;加拿大帕金森病协会的奖学金和拉瓦尔大学药学院教育与研究基金会(FER)的奖学金

Additive neurorestorative effects of exercise and docosahexaenoic acid intake in a mouse model of Parkinson’s disease

Olivier Kerdiles1, 2, 3, 4, #, Méryl-Farelle Oye Mintsa Mi-mba1, 2, 3, 4, #, Katherine Coulombe2, Cyntia Tremblay2, 4, Vincent Émond2, 4, Martine Saint-Pierre2, Clémence Rouxel2, 3, Line Berthiaume5, 6, Pierre Julien5, 6, Francesca Cicchetti2, 7, Frédéric Calon1, 2, 3, 4, *   

  1. 1Faculté de pharmacie, Université Laval, 1050 Avenue de la Médecine, Quebec, QC, Canada; 2Axe Neuroscience, Centre de recherche du CHU de Québec-Université Laval (Pavillon CHUL), 2705 Boulevard Laurier, Quebec, QC, Canada; 3Institute of Nutrition and Functional Foods, Quebec, QC, Canada; 4Optinutribrain International Associated Laboratory (NutriNeuro, France; INAF, Canada), Quebec, QC, Canada; 5Axe Endocrinologie et Néphrologie, Centre de recherche du CHU de Québec-Université Laval, Quebec, QC, Canada; 6Département de Médecine, Faculté de Médecine, Université Laval, Quebec, QC, Canada; 7Département de Psychiatrie et Neurosciences, Faculté de Médecine, Quebec, QC, Canada
  • Online:2025-02-15 Published:2024-06-18
  • Contact: Frédéric Calon, PhD, frederic.calon@crchudequebec.ulaval.ca.
  • Supported by:
    This study was supported by funding from Parkinson Canada. OK was funded by a scholarship from Parkinson Canada and a scholarship from Fonds d’Enseignement et de Recherche (FER) (Faculty of Pharmacy, Université Laval). FCa and FCi are both recipients of Researcher Chairs from the Fonds de Recherche du Québec en Santé (FRQS) providing salary support and operating funds.

摘要:

鉴于临床前和临床研究表明膳食中的 n-3 多不饱和脂肪酸(n-3 PUFA)(如二十二碳六烯酸)和运动对帕金森病有益,实验旨在进一步探讨两者是否能协同诱导多巴胺能通路的恢复。首先,向小鼠纹状体单侧立体定向注射6-羟基多巴胺建立帕金森病动物模型。二十二碳六烯酸治疗、自主运动或两者的结合对(i) 旷场实验中的活动距离、(ii)阿朴吗啡诱导试验中的逆转百分比或(iii)黑质致密部的酪氨酸羟化酶阳性细胞数量没有影响。然而,二十二碳六烯酸增加了酪氨酸羟化酶阳性神经元的数量,并诱导了病变纹状体中多巴胺水平的上升。与二十二碳六烯酸治疗或单独运动相比,二十二碳六烯酸结合运动(i)改善了踏步试验中前肢的平衡;(ii)降低了纹状体3,4-二羟基苯乙酸/多巴胺比率;(iii)促进病变纹状体中多巴胺转运体水平的增加。以上结果表明,运动结合二十二碳六烯酸可在单侧多巴胺能系统病变小鼠的纹状体中发挥协同作用,从而为营养结合体育锻炼治疗帕金森病的临床试验提供数据支持。

https://orcid.org/0000-0002-4203-0887 (Frédéric Calon)

Abstract: There is a need to develop interventions to slow or reverse the degeneration of dopamine neurons in Parkinson’s disease after diagnosis. Given that preclinical and clinical studies suggest benefits of dietary n-3 polyunsaturated fatty acids, such as docosahexaenoic acid, and exercise in Parkinson’s disease, we investigated whether both could synergistically interact to induce recovery of the dopaminergic pathway. First, mice received a unilateral stereotactic injection of 6-hydroxydopamine into the striatum to establish an animal model of nigrostriatal denervation. Four weeks after lesion, animals were fed a docosahexaenoic acid-enriched or a control diet for the next 8 weeks. During this period, the animals had access to a running wheel, which they could use or not. Docosahexaenoic acid treatment, voluntary exercise, or the combination of both had no effect on (i) distance traveled in the open field test, (ii) the percentage of contraversive rotations in the apomorphine-induction test or (iii) the number of tyrosine-hydroxylase-positive cells in the substantia nigra pars compacta. However, the docosahexaenoic acid diet increased the number of tyrosine-hydroxylase-positive terminals and induced a rise in dopamine concentrations in the lesioned striatum. Compared to docosahexaenoic acid treatment or exercise alone, the combination of docosahexaenoic acid and exercise (i) improved forelimb balance in the stepping test, (ii) decreased the striatal DOPAC/dopamine ratio and (iii) led to increased dopamine transporter levels in the lesioned striatum. The present results suggest that the combination of exercise and docosahexaenoic acid may act synergistically in the striatum of mice with a unilateral lesion of the dopaminergic system and provide support for clinical trials combining nutrition and physical exercise in the treatment of Parkinson’s disease.

Key words: 6-hydroxydopamine, dopamine, dopamine transporter, exercise, neurorestoration, Parkinson’s disease, polyunsaturated fatty acids omega-3