Marie Anaïs, Leroy Julien, Darricau Morgane, Alfos Serge, De Smedt-Peyrusse Veronique, Richard Emmanuel, Vancassel Sylvie, Bosch-Bouju Clementine
Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (INRAE), Institut Polytechnique de Bordeaux (INP), NutriNeuro, University of Bordeaux, Bordeaux, France.
Institut des Maladies Neurodégénératives, University of Bordeaux, Bordeaux, France.
Front Nutr. 2022 Feb 1;9:811843. doi: 10.3389/fnut.2022.811843. eCollection 2022.
The mechanisms leading to a loss of dopaminergic (DA) neurons from the substantia nigra (SNc) in Parkinson's disease (PD) have multifactorial origins. In this context, nutrition is currently investigated as a modifiable environmental factor for the prevention of PD. In particular, initial studies revealed the deleterious consequences of vitamin A signaling failure on dopamine-related motor behaviors. However, the potential of vitamin A supplementation itself to prevent neurodegeneration has not been established yet.
The hypothesis tested in this study is that preventive vitamin A supplementation can protect DA neurons in a rat model of PD.
The impact of a 5-week preventive supplementation with vitamin A (20 IU/g of diet) was measured on motor and neurobiological alterations induced by 6-hydroxydopamine (6-OHDA) unilateral injections in the striatum of rats. Rotarod, step test and cylinder tests were performed up to 3 weeks after the lesion. Post-mortem analyses (retinol and monoamines dosages, western blots, immunofluorescence) were performed to investigate neurobiological processes.
Vitamin A supplementation improved voluntary movements in the cylinder test. In 6-OHDA lesioned rats, a marked decrease of dopamine levels in striatum homogenates was measured. Tyrosine hydroxylase labeling in the SNc and in the striatum was significantly decreased by 6-OHDA injection, without effect of vitamin A. By contrast, vitamin A supplementation increased striatal expression of D2 and RXR receptors in the striatum of 6-OHDA lesioned rats.
Vitamin A supplementation partially alleviates motor alterations and improved striatal function, revealing a possible beneficial preventive approach for PD.
帕金森病（PD）中导致黑质致密部（SNc）多巴胺能（DA）神经元缺失的机制具有多因素起源。在此背景下，目前正在研究营养作为预防PD的可改变环境因素。特别是，初步研究揭示了维生素A信号传导失败对多巴胺相关运动行为的有害影响。然而，维生素A补充本身预防神经退行性变的潜力尚未确定。
本研究检验的假设是预防性补充维生素A可保护PD大鼠模型中的DA神经元。
测量了连续5周预防性补充维生素A（20 IU/g饮食）对大鼠纹状体单侧注射6-羟基多巴胺（6-OHDA）诱导的运动和神经生物学改变的影响。在损伤后长达3周进行转棒试验、阶梯试验和圆筒试验。进行死后分析（视黄醇和单胺剂量测定、蛋白质免疫印迹、免疫荧光）以研究神经生物学过程。
补充维生素A改善了圆筒试验中的自主运动。在6-OHDA损伤的大鼠中，测量到纹状体匀浆中多巴胺水平显著降低。6-OHDA注射使SNc和纹状体中的酪氨酸羟化酶标记显著降低，维生素A无此作用。相比之下，补充维生素A增加了6-OHDA损伤大鼠纹状体中D2和RXR受体的表达。
补充维生素A可部分缓解运动改变并改善纹状体功能，揭示了一种可能对PD有益的预防方法。
