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Quercetin mitigates monosodium glutamate-induced excitotoxicity of the spinal cord motoneurons in aged rats via p38 MAPK inhibition.
Acta Histochemica ( IF 2.5 ) Pub Date : 2020-05-20 , DOI: 10.1016/j.acthis.2020.151554
Alaa El-Din L Firgany 1 , Nahla Reda Sarhan 2
Affiliation  

Various studies reported the possibility of deterioration of blood–brain barrier (BBB) integrity owing to the aging process. The current work was performed to investigate the ability of Monosodium glutamate (MSG) to cross BBB in aged rats, the damage affecting the anterior horn cells of the spinal cord due to excitotoxicity, and the mechanisms by which quercetin (Que) administration might suppress such damage.

Forty male rats aged 18 months were assigned equally to 4 groups: control group, Que group (received Que, 20 mg/kg/d intraperitonealy for 10 days), MSG group (received MSG, 4.0 g/kg/d subcutaneously for 10 days), MSG + Que group (received both Que and MSG as done in the Que and MSG groups respectively). Cervical spinal cord specimens were obtained and prepared for routine histological study, immunohistochemical staining by caspase-3 and glial fibrillary acidic protein (GFAP), assessment of oxidative stress, measurement of cytokines, assessment of caspase-3 activity and GFAP levels as well as for western blotting of phosphorylated activating transcription factor 2 (ATF2pp) as an indicator for the activity of p38 mitogen-activated protein kinase (MAPK).

The MSG group revealed variable degenerative and apoptotic changes in the motoneurons and neuroglia, a marked rise in the cytoplasmic caspase-3 expression in motoneurons and a significant reduction (p < 0.001) in the astrocyte surface area percentage. In addition, the spinal cord tissue exhibited a significant elevation (p < 0.001) in the levels of malondialdehyde (MDA), IL-1, IL-6, TNFα, INFɣ, caspase-3 activity and ATF2 pp expression as well as a significant reduction (p < 0.001) in SOD, IL-10 and GFAP levels compared with the control group. On combining Que with MSG, most of the degenerative changes were reversed and all the impaired parameters were nearly normalized except for IL-6 and GFAP levels which were still significantly (p < 0.05) different from those of the control group. Our study suggests that MSG can break through the BBB of the aged rats and induce excitotoxicity dependent changes in spinal cord motoneurons. Most of these changes were reversed by Que probably via targeting the p38 MAPK-ATF2 pathway, antagonizing oxidative stress, anti-inflammatory effect, and promoting GFAP expression.



中文翻译:

槲皮素通过抑制p38 MAPK减轻老年大鼠中味精对脊髓运动神经元的兴奋性毒性。

各种研究报告说,由于老化过程,血脑屏障(BBB)完整性可能会降低。目前的工作是研究谷氨酸钠(MSG)穿过老年大鼠的BBB能力,由于兴奋性毒性而影响脊髓前角细胞的损伤以及槲皮素(Que)给药可能抑制这种作用的机制。损伤。

将40只18个月大的雄性大鼠平均分为4组:对照组,Que组(接受Que,腹膜内接受20 mg / kg / d,持续10天),MSG组(接受MSG,4.0 g / kg / d,皮下接受10天)。 ),MSG + Que组(分别在Que和MSG组中接收到Que和MSG)。获得宫颈脊髓标本并准备用于常规组织学研究,caspase-3和神经胶质原纤维酸性蛋白(GFAP)的免疫组织化学染色,氧化应激评估,细胞因子测量,caspase-3活性和GFAP水平评估以及磷酸化的活化转录因子2(ATF2 pp)的蛋白质印迹作为p38丝裂原活化蛋白激酶(MAPK)活性的指标。

味精组揭示了运动神经元和神经胶质细胞的变性和凋亡变化,运动神经元中胞浆caspase-3表达的显着增加以及星形胶质细胞表面积百分比的显着降低(p <0.001)。此外,脊髓组织的丙二醛(MDA),IL-1,IL-6,TNFα,INFɣ,caspase-3活性和ATF2 pp表达水平显着升高(p <0.001),并且与对照组相比,SOD,IL-10和GFAP水平降低(p <0.001)。将Que与MSG结合使用后,大部分的变性变化都可以逆转,并且所有受损的参数几乎都已归一化,除了IL-6和GFAP水平仍然很明显(p <0.05)与对照组的差异。我们的研究表明,味精可以突破老年大鼠的血脑屏障,并诱发脊髓运动神经元的兴奋性毒性依赖性变化。Que可能通过靶向p38 MAPK-ATF2途径,拮抗氧化应激,抗炎作用和促进GFAP表达而逆转了大多数这些变化。

更新日期:2020-05-20
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