Glucagon-like peptide-1 (GLP-1) is a hormone mainly secreted from enteroendocrine L cells. GLP-1 and its receptor are also expressed in the brain. GLP-1 signaling has pivotal roles in regulating neuroinflammation and memory function, but it is unclear how GLP-1 improves memory function by regulating neuroinflammation. Here, we demonstrated that GLP-1 enhances neural structure by inhibiting lipopolysaccharide (LPS)-induced inflammation in microglia with the effects of GLP-1 itself on neurons. Inflammatory secretions of BV-2 microglia by LPS aggravated mitochondrial function and cell survival, as well as neural structure in Neuro-2a neurons. In inflammatory condition, GLP-1 suppressed the secretion of tumor necrosis factor-alpha (TNF-α)-associated cytokines and chemokines in BV-2 microglia and ultimately enhanced neurite complexity (neurite length, number of neurites from soma, and secondary branches) in Neuro-2a neurons. We confirmed that GLP-1 improves neurite complexity, dendritic spine morphogenesis, and spine development in TNF-α-treated primary cortical neurons based on altered expression levels of the factors related to neurite growth and spine morphology. Given that our data that GLP-1 itself enhances neurite complexity and spine morphology in neurons, we suggest that GLP-1 has a therapeutic potential in central nervous system diseases.

译文

:胰高血糖素样肽1(GLP-1)是一种主要从肠内分泌L细胞分泌的激素。 GLP-1及其受体也在大脑中表达。 GLP-1信号在调节神经炎症和记忆功能中起着关键作用,但目前尚不清楚GLP-1如何通过调节神经炎症来改善记忆功能。在这里,我们证明了GLP-1通过抑制脂多糖(LPS)诱导的小胶质细胞炎症增强了神经结构,其中GLP-1本身对神经元有影响。 LPS引起的BV-2小胶质细胞的炎性分泌物加剧了线粒体功能和细胞存活,以及Neuro-2a神经元的神经结构。在炎症状态下,GLP-1抑制了BV-2小胶质细胞中与肿瘤坏死因子-α(TNF-α)相关的细胞因子和趋化因子的分泌,并最终增强了神经突的复杂性(神经突的长度,来自体细胞的神经突的数量以及次级分支)。在Neuro-2a神经元中。我们证实,基于与神经突生长和脊柱形态有关的因子的表达水平改变,GLP-1可改善TNF-α治疗的原代皮层神经元的神经突复杂性,树突状棘形态和脊柱发育。鉴于我们的数据表明GLP-1本身会增强神经元的神经突复杂性和脊柱形态,因此我们建议GLP-1在中枢神经系统疾病中具有治疗潜力。

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