Sodium butyrate exerts protective effect against Parkinson's disease in mice via stimulation of glucagon like peptide-1
Sodium butyrate exerts protective effect against Parkinson's disease in mice via stimulation of glucagon like peptide-1
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DOI：
10.1016/j.jns.2017.08.3235
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发表时间：
2017-10-15
影响因子：
4.4
通讯作者：
Sun, Jing
中科院分区：
文献类型：
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作者：
Liu, Jiaming;Wang, Fangyan;Sun, Jing
丁酸钠(NAB)在神经系统疾病中表现出保护作用。在这里，我们研究了NAB在帕金森病(PD)小鼠模型中的神经保护作用和可能的机制。小鼠连续7d腹腔注射MPTP(30 mg/kg)建立帕金森病模型，NAB(200 mg/kg)灌胃治疗3周。然后进行了行为测试。用免疫印迹和酪氨酸羟化酶免疫组织化学方法检测黑质多巴胺能神经元的变性。通过组织学(Nissl细胞死亡染色)、凋亡相关蛋白和紧密连接(TJ)蛋白的研究来评估脑损伤。同时检测结肠高血糖素样多肽-1(GLP-1)和脑GLP-1受体(GLP-1R)的表达水平。我们的结果表明，NAB改善了神经行为障碍，包括认知行为和协调能力。此外，NAB治疗可防止MPTP诱导的多巴胺能变性，并降低纹状体TH的表达水平。NAB治疗可通过上调阻滞素和阻塞性小带(ZO)-1的表达来减轻PD对血脑屏障的破坏。此外，NAB还导致Bc l-2水平升高，Bax水平降低。特别是，NAB治疗的帕金森病小鼠与帕金森病组相比，结肠GLP-1水平升高，脑GLP-1R表达上调。我们的研究结果表明，NAB有可能成为治疗PD的一种新的治疗方法，其机制与刺激结肠GLP-1的分泌有关。
Sodium butyrate (NaB) has exhibited protective activity in neurological disorders. Here, we investigated the neuroprotective effect and potential mechanisms of NaB in a mouse model of Parkinson's disease (PD). A mouse was intraperitoneally treated with MPTP (30 mg/kg) for 7 consecutive days to induce PD model and NaB (200 mg/kg) was intragastrically treated for 3 weeks. The behavioral tests were then conducted. Dopaminergic degeneration was evaluated by western blot and immunohistochemistry of tyrosine hydroxylase (TH) in the SN. Brain damage was assessed by histologic (Nissl staining for cell death), apoptosis-associated protein and tight junction (TJ) proteins studies. Meanwhile, the levels of colonic glucagon-like peptide-1 (GLP-1) and cerebral GLP-1 receptor (GLP-1R) expression were assessed. Our results showed that NaB improved neurobehavioral impairment including cognitive behavior and coordination performance. Moreover, NaB treatment prevented the MPTP-induced dopaminergic degeneration and decreased expression level of TH in the striatum. NaB treatment attenuated the PD-associated disruption of BBB by upregulation of Occludin and zonula occludens (ZO)-1. In addition, NaB resulted in increased level of Bcl-2 and decreased level of Bax. Particularly, NaB-treated mice with PD exhibited increased colonic GLP-1 level as well as upregulation of brain GLP-1R expression compared with PD group. Our findings suggest that NaB has potential as a novel therapeutic for treatment of PD, and its mechanism was associated with stimulating colonic GLP-1 secretion.