da Costa Roberta Oliveira, Gadelha-Filho Carlos Vinicius Jataí, de Aquino Pedro Everson Alexandre, Lima Ludmila Araújo Rodrigues, de Lucena Jalles Dantas, Ribeiro Wesley Lyeverton Correia, Lima Francisco Arnaldo Viana, Neves Kelly Rose Tavares, de Barros Viana Glauce Socorro
Graduate Program of Morphofunctional Sciences, Faculty of Medicine of the Federal University of Ceará, Fortaleza, Brazil.
Graduate Program of Pharmacology, Faculty of Medicine of the Federal University of Ceará, Fortaleza, Brazil.
Neurochem Res. 2023 Jan;48(1):142-160. doi: 10.1007/s11064-022-03728-4. Epub 2022 Aug 26.
In the present study, we investigated the effects of physical exercise in the presence of Vitamin D3 (VD3), on 6-hydroxydopamine (6-OHDA)-lesioned hemiparkinsonian rats. The animals were divided into sham-operated (SO), 6-OHDA-lesioned, and 6-OHDA-lesioned plus VD3 (1 µg/kg, 21 days), in the absence (no exercise, NE) and presence (with exercise, WE) of physical exercise on a treadmill (30 min, speed of 20 cm/s, once a day/21 days). This procedure started, 24 h after the stereotaxic surgery (injections of 6-OHDA into the right striatum). The animals were then subjected to behavioral (rotarod, open field, and apomorphine tests) and their brain areas were dissected for neurochemical, dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC) determinations, and immunohistochemical studies for tyrosine hydroxylase (TH), dopamine transporter (DAT), and vitamin D receptor (VD3R). The effects on the brain oxidative stress: nitrite/nitrate, glutathione (GSH), and malondialdehyde (MDA) measurements were also evaluated. Behavioral changes of the 6-OHDA lesioned group were improved by exercise plus VD3. Similar results were observed in dopamine (DA) and 3,4-dihydroxyphenylacetic acid (DOPAC) concentrations increased by exercise and VD3, compared with SO groups. Additionally, tyrosine hydroxylase (TH) and dopamine transporter (DAT) immunoexpressions were decreased in the 6-OHDA-lesioned groups, with values normalized after exercise and VD3. The VD3 receptor immunoexpression decreased in the 6-OHDA (NE) group, and this was attenuated by exercise, especially after VD3. While 6-OHDA lesions increased, VD3 supplementation decreased the oxidative stress, which was intensified by exercise. VD3 showed neuroprotective properties that were intensified by physical exercise. These VD3 actions on hemiparkinsonian rats are possibly related to its antioxidant and anti-inflammatory effects.
在本研究中，我们调查了在维生素D3（VD3）存在的情况下，体育锻炼对6-羟基多巴胺（6-OHDA）损伤的偏侧帕金森病大鼠的影响。将动物分为假手术组（SO）、6-OHDA损伤组，以及6-OHDA损伤加VD3组（1μg/kg，21天），分别处于无体育锻炼（无运动，NE）和有体育锻炼（有运动，WE）的状态，体育锻炼在跑步机上进行（30分钟，速度20厘米/秒，每天一次/共21天）。该程序在立体定向手术后24小时开始（将6-OHDA注射到右侧纹状体）。然后对动物进行行为学测试（转棒试验、旷场试验和阿扑吗啡试验），并解剖其脑区进行神经化学分析，测定多巴胺（DA）、3,4-二羟基苯乙酸（DOPAC），并对酪氨酸羟化酶（TH）、多巴胺转运体（DAT）和维生素D受体（VD3R）进行免疫组织化学研究。还评估了对脑氧化应激的影响：亚硝酸盐/硝酸盐、谷胱甘肽（GSH）和丙二醛（MDA）的测量。运动加VD3改善了6-OHDA损伤组的行为变化。与SO组相比，运动和VD3使多巴胺（DA）和3,4-二羟基苯乙酸（DOPAC）浓度增加，观察到了类似结果。此外，6-OHDA损伤组中酪氨酸羟化酶（TH）和多巴胺转运体（DAT）的免疫表达降低，运动和VD3后其值恢复正常。6-OHDA（NE）组中VD3受体免疫表达降低，运动可使其减弱，尤其是在补充VD3后。虽然6-OHDA损伤增加，但补充VD3可降低氧化应激，运动可加剧这种氧化应激。VD3具有神经保护特性，体育锻炼可增强这些特性。VD3对偏侧帕金森病大鼠的这些作用可能与其抗氧化和抗炎作用有关。
