Activation of Sonic hedgehog signal by Purmorphamine, in a mouse model of Parkinson's disease, protects dopaminergic neurons and attenuates inflammatory response by mediating PI3K/AKt signaling pathway

Shao,Shuai; Wang,Guang‑Liang; Raymond,Cespuglio; Deng,Xue‑Hua; Zhu,Xiao‑Lan; Wang,Di; Hong,Le‑Peng

doi:10.3892/mmr.2017.6751

Activation of Sonic hedgehog signal by Purmorphamine, in a mouse model of Parkinson's disease, protects dopaminergic neurons and attenuates inflammatory response by mediating PI3K/AKt signaling pathway

Authors:
- Shuai Shao
- Guang‑Liang Wang
- Cespuglio Raymond
- Xue‑Hua Deng
- Xiao‑Lan Zhu
- Di Wang
- Le‑Peng Hong
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Affiliations: Department of Anatomy, Guangzhou Medical University, Guangzhou, Guangdong 511436, P.R. China, Department of Histology and Embryology, Guangzhou Medical University, Guangzhou, Guangdong 511436, P.R. China, Neuroscience Research Center of Lyon (CRNL), Neurochem, Claude Bernard University, F-69373 Lyon, France, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 511436, P.R. China
Published online on: June 9, 2017 https://doi.org/10.3892/mmr.2017.6751
Pages: 1269-1277
Copyright: © Shao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

In Parkinson's disease (PD), microglial activation-mediated neuroinflammation is associated with dopaminergic neurons degeneration in the substantia nigra pars compacta. Previous studies that have investigated this neurodegenerative disease have reported that the Sonic hedgehog (SHH) signaling pathway, through inhibiting the inflammatory processes, exerts a beneficial neuroprotective effect. However, the mechanisms underlying the anti‑inflammatory and neuroprotective effects of this signaling pathway remain poorly understood. The present study aimed to further investigate these mechanisms in vitro and in vivo. At first, BV2 microglial cells treated with lipopolysaccharide (LPS) were used to induce an inflammatory response. It was observed that the activation of SHH signaling by Purmorphamine attenuated the LPS‑induced inflammatory response, increased the expression of transforming growth factor‑β1 through the phosphatidylinositol 3‑kinase (PI3K)/AKT serine/threonine kinase (Akt) intracellular signaling pathway and inhibited nuclear receptor subfamily 4 group A member 2, independently of the PI3K/Akt signaling pathway. Furthermore, the blockade of the PI3K/Akt signaling pathway by intranasal administration of LY294002, significantly reduced the SHH‑associated neuroprotective effects on dopaminergic neurons, improved motor functions, and increased the microglial activation and inflammatory response in a mouse model of PD induced using 1‑methyl‑4‑phenyl‑1,2,3,6‑tetrahydropyridine. In conclusion, the data of the present study reported that anti‑inflammatory and neuroprotective effects can be obtained in BV2 microglial cells and in a mouse model of PD by successive activation of the SHH and PI3K/Akt signaling pathways.

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