Retinoic Acid Prevents the Neuronal Damage Through the Regulation of Parvalbumin in an Ischemic Stroke Model
Retinoic Acid Prevents the Neuronal Damage Through the Regulation of Parvalbumin in an Ischemic Stroke Model
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DOI：
10.1007/s11064-022-03769-9
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发表时间：
2022-10-16
影响因子：
4.4
通讯作者：
Koh，Phil-Ok
中科院分区：
文献类型：
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作者：
Kang，Ju-Bin;Park，Dong-Ju;Koh，Phil-Ok
缺血性中风是一种神经系统疾病，通过增加氧化应激和离子失衡引起脑损伤。视黄酸是维生素A的主要代谢产物，调节氧化应激、钙稳态和细胞死亡。细胞内钙参与神经元的生长和突触可塑性。小清蛋白是一种钙结合蛋白，主要在脑中表达。在这项研究中，我们调查是否维甲酸具有神经保护作用，通过控制细胞内钙离子浓度和小白蛋白表达缺血性脑损伤。采用大脑中动脉闭塞（MCAO）法诱导脑缺血。手术前4天腹腔注射维甲酸（5 mg/kg）或溶媒，MCAO后24 h收集大脑皮质用于进一步研究。MCAO损伤诱导神经功能缺损和组织病理学改变，并降低小白蛋白表达。然而，维甲酸治疗缓解了这些变化。在培养的神经元中，谷氨酸（5 mM）暴露诱导神经元细胞死亡，增加细胞内钙离子浓度，并降低小清蛋白表达。视黄酸处理以剂量依赖性方式减弱了这些对谷氨酸毒性的变化。它还调节谷氨酸诱导的bcl-2和bax表达的变化。在非转染条件下，视黄酸的缓解作用大于在小白蛋白siRNA转染条件下。我们的研究结果表明，视黄酸调节细胞内钙离子浓度和小白蛋白的表达，并防止缺血性脑损伤的细胞凋亡。总之，维甲酸通过控制小白蛋白表达和凋亡相关蛋白，有助于保护缺血性卒中神经元。
Ischemic stroke is a neurological disease that causes brain damage by increasing oxidative stress and ion imbalance. Retinoic acid is a major metabolite of vitamin A and regulates oxidative stress, calcium homeostasis, and cell death. Intracellular calcium is involved in neuronal growth and synaptic plasticity. Parvalbumin is a calcium-binding protein that is mainly expressed in brain. In this study, we investigated whether retinoic acid has neuroprotective effects by controlling intracellular calcium concentration and parvalbumin expression in ischemic brain damage. Middle cerebral artery occlusion (MCAO) was performed to induce cerebral ischemia. Retinoic acid (5 mg/kg) or vehicle was injected into the abdominal cavity for four days before surgery and cerebral cortices were collected 24 h after MCAO for further studies. MCAO damage induced neurological deficits and histopathological changes and decreased parvalbumin expression. However, retinoic acid treatment alleviated these changes. In cultured neurons, glutamate (5 mM) exposure induced neuronal cell death, increased intracellular calcium concentration, and decreased parvalbumin expression. Retinoic acid treatment attenuated these changes against glutamate toxicity in a dose-dependent manner. It also regulates glutamate induced change in bcl-2 and bax expression. The mitigation effects of retinoic acid were greater under non-transfection conditions than under parvalbumin siRNA transfection conditions. Our findings showed that retinoic acid modulates intracellular calcium concentration and parvalbumin expression and prevents apoptosis in ischemic brain injury. In conclusion, retinoic acid contributes to the preservation of neurons from ischemic stroke by controlling parvalbumin expression and apoptosis-related proteins.