Somatostatin prevents lipopolysaccharide-induced neurodegeneration in the rat substantia nigra by inhibiting the activation of microglia.
Somatostatin prevents lipopolysaccharide-induced neurodegeneration in the rat substantia nigra by inhibiting the activation of microglia.
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DOI：
10.3892/mmr.2015.3494
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发表时间：
2015-07
影响因子：
3.4
通讯作者：
Ren Y
中科院分区：
文献类型：
--
作者：
Bai L;Zhang X;Li X;Liu N;Lou F;Ma H;Luo X;Ren Y
生长抑素（SST）是一种在中枢神经系统（CNS）中含量丰富的神经调质，在神经退行性疾病中起着至关重要的作用。然而，关于SST在帕金森病（PD）背景下对多巴胺（DA）能神经元的作用和机制知之甚少。本研究采用内毒素（lipopolysaccharide，LPS）注入大鼠黑质（substantia nigra，SN）建立PD模型，观察SST对LPS诱导的DA在体变性的影响。壁内注射LPS导致DA神经元的显着损失，而SST预处理的神经元死亡的减少，证实使用酪氨酸羟化酶和尼氏染色的免疫组织化学染色。同时，OX-42的免疫组织化学检测和氢乙啶染色分别用于确定小胶质细胞的活化和活性氧（ROS）的产生。结果表明，SST抑制LPS诱导的小胶质细胞活性和ROS的产生。ELISA显示，当在LPS处理之前给予SST时，促炎介质包括肿瘤坏死因子-α、白细胞介素-1 β和前列腺素E2的产生减少。Western blot分析显示，LPS诱导的诱导型一氧化氮合酶、环氧合酶2和核因子κ B（NF-κ B）p-p65的表达通过在LPS应用之前给予SST而减弱。结果表明，SST可抑制LPS诱导的黑质DA能神经元丢失，其神经保护作用与抑制小胶质细胞活化和NF-κ B通路有关，从而减轻神经炎症和氧化应激。因此，本研究表明SST通过抑制小胶质细胞的活化而有益于治疗神经退行性疾病，如PD。
Somatostatin (SST) is a neuromodulator which is abundant throughout the central nervous system (CNS) and has a crucial role in neurodegenerative disorders. However, little is known about the effects and mechanisms of SST in dopaminergic (DA) neurons in the context of Parkinson’s disease (PD). In the present study, a model of PD was generated by injecting lipopolysaccharide (LPS) into the substantia nigra (SN) of rats in order to investigate the effects of SST on LPS-induced degeneration of DA in vivo. Intramural injection of LPS resulted in a significant loss of DA neurons, while reduction of neuronal death by SST pretreatment was confirmed using immunohistochemical staining for tyrosine hydroxylase and Nissl. In parallel, immunohistochemical detection of OX-42 and hydroethidine staining were employed to determine the activation of microglia and production of reactive oxygen species (ROS), respectively. It was found that SST inhibited the LPS-induced microglial activity and ROS production. ELISA revealed a decreased production of pro-inflammatory mediators, including tumor necrosis factor-α, interleukin-1β and prostaglandin E2 when SST was administered prior to LPS treatment. Western blot analysis showed that LPS-induced expression of inducible nitric oxide synthase, cyclooxygenase-2 and nuclear factor κB (NF-κB) p-p65 was attenuated by administration of SST prior to LPS application. The results indicated that LPS-induced loss of nigral DA neurons was inhibited by SST and the observed effects of SST on neuroprotection were associated with suppression of microglial activation and the NF-κB pathway, ensuing decreases of neuroinflammation and oxidative stress. The present study therefore suggested that SST is beneficial for treating neurodegenerative diseases, such as PD, through inhibiting the activation of microglia.
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影响因子：
6.1
作者：
Tansey MG;Goldberg MS
通讯作者：
Goldberg MS
低剂量1-甲基-4-苯基-1,2,3,6-四氢吡啶会在核因子-κB报告小鼠中引起星形胶质细胞的炎症激活，然后再失去多巴胺能神经元。
影响因子：
4.2
作者：
Miller JA;Trout BR;Sullivan KA;Bialecki RA;Roberts RA;Tjalkens RB
通讯作者：
Tjalkens RB
DOI：
10.1007/bf02259660
发表时间：
1995-01-01
期刊：
JOURNAL OF NEURAL TRANSMISSION-PARKINSONS DISEASE AND DEMENTIA SECTION
影响因子：
--
作者：
ESPINO, A;CALOPA, M;NAVARRO, MA
通讯作者：
NAVARRO, MA
影响因子：
4.1
作者：
Phani, Sudarshan;Loike, John D;Przedborski, Serge
通讯作者：
Przedborski, Serge
影响因子：
2.9
作者：
Chung, Eun S.;Chung, Young C.;Jin, Byung K.
通讯作者：
Jin, Byung K.