Chronic Vanadium Exposure Promotes Aggregation of Alpha-Synuclein, Tau and Amyloid Beta in Mouse Brain

IF 4.2 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
O. R. Folarin, F. E. Olopade, T. T. Gilbert, A. D. Ladagu, P. I. Pires dos Santos, O. A. Mustapha, L. Z. Kpasham, J. O. Olopade, T. F. Outeiro
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引用次数: 0

Abstract

The interaction of toxic environmental metals and metalloids with brain proteins and polypeptides can result in pathological aggregations and formation of toxic oligomers, which are key features of many neurodegenerative diseases. Occupational and environmental exposure to vanadium is connected to a neurological syndrome that includes psychiatric symptoms, cognitive decline, and neurodegeneration. In this study, we hypothesized that prolonged vanadium exposure may be a potential risk factor for Alzheimer's and Parkinson's diseases. A total of 72 male BALB/c mice, each 4 weeks' old, were used. Vanadium-treated groups received intraperitoneal injections of 3 mg/kg body weight of vanadium three times a week for 6, 12, or 18 months. The control group received sterile water while the withdrawal group were given vanadium injection for 3 months, followed by withdrawal of the metal, but treatment with sterile water only, and were sacrificed at 3-, 9-, or 15-months post vanadium exposure. Sagittal sections of brain paraffin-embedded tissue were prepared and analyzed using immunofluorescence to study the immunoreactivity and cellular localization of α-synuclein (α-syn), amyloid-β (Aβ), and tau proteins. Our findings revealed pathological aggregation of these proteins in the frontoparietal cortices and the dorsal CA1 and CA3 regions. Double immunolabeling with glial cells and neurons showed neuronal degeneration, functional gliosis, and activation of astrocytes and microglia at sites of α-synuclein immunoreactivity. We observed increased immunoreactivity of phosphorylated nuclei tau both in the parietal cortices and corpus callosum white matter while we observed intraneuronal accumulation of Aβ deposits in the cortex and dorsal hippocampal regions in vanadium treated brains. These cellular changes and proteinopathies, although persisting, were significantly attenuated after vanadium withdrawal. Our findings show that prolonged vanadium exposure promotes abnormal accumulation of neurodegeneration-associated proteins (α-syn, Tau, and Aβ) in the brain, which is further exacerbated by aging in the context of extended exposure to the metal.

Abstract Image

慢性钒暴露促进小鼠脑内α -突触核蛋白、Tau蛋白和淀粉样蛋白的聚集
有毒环境金属和类金属与脑蛋白和多肽的相互作用可导致毒性低聚物的病理聚集和形成,这是许多神经退行性疾病的关键特征。职业性和环境性钒暴露与包括精神症状、认知能力下降和神经退行性变在内的神经系统综合征有关。在这项研究中,我们假设长时间的钒暴露可能是阿尔茨海默病和帕金森病的潜在危险因素。选用雄性BALB/c小鼠72只,每只4周龄。钒处理组每周3次腹腔注射3 mg/kg体重的钒,连续注射6、12、18个月。对照组给予无菌水,戒断组给予注射钒3个月后取出金属,但仅用无菌水治疗,并于钒暴露后3、9、15个月处死。制备脑石蜡包埋组织矢状面切片,利用免疫荧光技术研究α-突触核蛋白(α-syn)、淀粉样蛋白-β (Aβ)和tau蛋白的免疫反应性和细胞定位。我们的发现揭示了这些蛋白在额顶叶皮层和CA1和CA3背侧区域的病理聚集。胶质细胞和神经元的双重免疫标记显示神经元变性,功能性胶质细胞,α-突触核蛋白免疫反应部位的星形胶质细胞和小胶质细胞活化。我们观察到顶皮层和胼胝体白质中磷酸化的tau核的免疫反应性增加,而在钒处理的大脑中,我们观察到皮层和海马背区神经元内Aβ沉积的积累。这些细胞变化和蛋白质病变虽然持续存在,但在脱钒后明显减弱。我们的研究结果表明,长时间的钒暴露会促进大脑中神经变性相关蛋白(α-syn、Tau和Aβ)的异常积累,而在长时间暴露于钒的情况下,这种情况会进一步加剧。
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来源期刊
Journal of Neurochemistry
Journal of Neurochemistry 医学-神经科学
CiteScore
9.30
自引率
2.10%
发文量
181
审稿时长
2.2 months
期刊介绍: Journal of Neurochemistry focuses on molecular, cellular and biochemical aspects of the nervous system, the pathogenesis of neurological disorders and the development of disease specific biomarkers. It is devoted to the prompt publication of original findings of the highest scientific priority and value that provide novel mechanistic insights, represent a clear advance over previous studies and have the potential to generate exciting future research.
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