Exploring the reduction in aquaporin-4 and increased expression of ciliary neurotrophic factor with the frontal-striatal gliosis induced by chronic high-fat dietary stress.

IF 4.2 3区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Jing-Ting Fu, Hui-Ting Huang, Pei-Chun Chen, Yu-Min Kuo, Po-See Chen, Shun-Fen Tzeng
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引用次数: 0

Abstract

High-fat diet (HFD)-induced obesity induces peripheral inflammation and hypothalamic pathogenesis linking the activation of astrocytes and microglia. Clinical evidence indicates a positive correlation between obesity and psychiatric disorders, such as depression. The connectivity of the frontal-striatal (FS) circuit, involving the caudate putamen (CPu) and anterior cingulate cortex (ACC) within the prefrontal cortex (PFC), is known for its role in stress-induced depression. Thus, there is a need for a thorough investigation into whether chronic obesity-induced gliosis, characterized by the activation of astrocytes and microglia, in these brain regions of individuals with chronic obesity. The results revealed increased S100β+ astrocytes and Iba1+ microglia in the CPu and ACC of male obese mice, along with immune cell accumulation in meningeal lymphatic drainage. Activated GFAP+ astrocytes and Iba1+ microglia were observed in the corpus callosum of obese mice. Gliosis in the CPu and ACC was linked to elevated cleaved caspase-3 levels, indicating potential neural cell death by chronic HFD feeding. There was a loss of myelin and adenomatous polyposis coli (APC)+ oligodendrocytes (OLs) in the corpus callosum, an area known to be linked with injury to the CPu. Additionally, reduced levels of aquaporin-4 (AQP4), a protein associated within the glymphatic systems, were noted in the CPu and ACC, while ciliary neurotrophic factor (CNTF) gene expression was upregulated in these brain regions of obese mice. The in vitro study revealed that high-dose CNTF causing a trend of reduced astrocytic AQP4 expression, but it significantly impaired OL maturation. This pathological evidence highlights that prolonged HFD consumption induces persistent FS gliosis and demyelination in the corpus callosum. An elevated level of CNTF appears to act as a potential regulator, leading to AQP4 downregulation in the FS areas and demyelination in the corpus callosum. This cascade of events might contribute to neural cell damage within these regions and disrupt the glymphatic flow.

探究长期高脂饮食压力诱发额叶-纹状体胶质细胞病变与水通道蛋白-4减少和睫状神经营养因子表达增加的关系
高脂饮食(HFD)引起的肥胖会诱发外周炎症和下丘脑发病机制,并与星形胶质细胞和小胶质细胞的活化有关。临床证据表明,肥胖与抑郁症等精神疾病之间存在正相关。额叶-纹状体(FS)回路的连接涉及前额叶皮层(PFC)内的尾状丘脑(CPu)和前扣带回皮层(ACC)。因此,有必要深入研究慢性肥胖患者的这些脑区是否存在以星形胶质细胞和小胶质细胞活化为特征的慢性肥胖诱导的神经胶质病变。结果发现,雄性肥胖小鼠 CPu 和 ACC 中的 S100β+ 星形胶质细胞和 Iba1+ 小胶质细胞增多,同时脑膜淋巴引流中的免疫细胞聚集。在肥胖小鼠的胼胝体中观察到活化的 GFAP+星形胶质细胞和 Iba1+小胶质细胞。CPu和ACC的神经胶质增生与裂解的caspase-3水平升高有关,表明长期摄入高脂低糖可能导致神经细胞死亡。胼胝体中出现了髓鞘和腺瘤性息肉病大肠杆菌(APC)+少突胶质细胞(OLs)的缺失,而这一区域已知与CPu的损伤有关。此外,在肥胖小鼠的 CPu 和 ACC 中还发现了与甘液系统相关的蛋白 Aquaporin-4 (AQP4)水平降低,而睫状神经营养因子 (CNTF) 基因表达在肥胖小鼠的这些脑区上调。体外研究显示,大剂量 CNTF 会导致星形胶质细胞 AQP4 表达减少,但会显著影响 OL 的成熟。这些病理证据突出表明,长期摄入高纤维食物会诱发胼胝体持续性FS胶质增生和脱髓鞘。CNTF 水平的升高似乎是一个潜在的调节因子,导致 FS 区域的 AQP4 下调和胼胝体的脱髓鞘。这一系列事件可能会导致这些区域的神经细胞受损,并破坏血流。
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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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