Somatostatin prevents lipopolysaccharide‑induced neurodegeneration in the rat substantia nigra by inhibiting the activation of microglia

Bai,Lijuan; Zhang,Xique; Li,Xiaohong; Liu,Na; Lou,Fan; Ma,Honglei; Luo,Xiaoguang; Ren,Yan

doi:10.3892/mmr.2015.3494

Somatostatin prevents lipopolysaccharide‑induced neurodegeneration in the rat substantia nigra by inhibiting the activation of microglia

Authors:
- Lijuan Bai
- Xique Zhang
- Xiaohong Li
- Na Liu
- Fan Lou
- Honglei Ma
- Xiaoguang Luo
- Yan Ren
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Affiliations: Department of Neurology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China
Published online on: March 13, 2015 https://doi.org/10.3892/mmr.2015.3494
Pages: 1002-1008
Copyright: © Bai et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

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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