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| Content Provider | Springer Nature : BioMed Central |
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| Author | Fu, Shou-Peng Wang, Jian-Fa Xue, Wen-Jing Liu, Hong-Mei Liu, Bing-run Zeng, Ya-Long Li, Su-Nan Huang, Bing-Xu Lv, Qing-Kang Wang, Wei Liu, Ju-Xiong |
| Abstract | Background Accumulating evidence suggests that neuroinflammation plays an important role in the progression of Parkinson’s disease (PD). Excessively activated microglia produce several pro-inflammatory enzymes and pro-inflammatory cytokines, leading to damage to surrounding neurons and eventually inducing neurodegeneration. Therefore, the inhibition of microglial overactivation may be a potential therapeutic strategy to prevent the further progression of PD. β-Hydroxybutyric acid (BHBA) has been shown to suppress lipopolysaccharide (LPS)-induced inflammation in BV-2 cells and to protect dopaminergic neurons in previous studies, but the underlying mechanisms remain unclear. Thus, in this study, we further investigated this mechanism in LPS-induced in vivo and in vitro PD models. Methods For the in vitro experiments, primary mesencephalic neuron-glia cultures were pretreated with BHBA and stimulated with LPS. [3H]dopamine (DA) uptake, tyrosine hydroxylase-immunoreactive (TH-ir) neurons and morphological analysis were evaluated and analyzed in primary mesencephalic neuron-glia cultures. In vivo, microglial activation and the injury of dopaminergic neurons were induced by LPS intranigral injection, and the effects of BHBA treatment on microglial activation and the survival ratio and function of dopaminergic neurons were investigated. Four our in vitro mechanistic experiment, primary microglial cells were pretreated with BHBA and stimulated with LPS; the cells were then assessed for the responses of pro-inflammatory enzymes and pro-inflammatory cytokines, and the NF-κB signaling pathway was evaluated and analyzed. Results We found that BHBA concentration-dependently attenuated the LPS-induced decrease in [3H]DA uptake and loss of TH-ir neurons in the primary mesencephalic neuron/glia mixed culture. BHBA treatment significantly improved the motor dysfunction of the PD model rats induced by intranigral injection of LPS, and this beneficial effect of BHBA was attributed to the inhibition of microglial overactivation and the protection of dopaminergic neurons in the substantia nigra (SN). Our in vitro mechanistic study revealed that the inhibitory effect of BHBA on microglia was mediated by G-protein-coupled receptor 109A (GPR109A) and involved the NF-κB signaling pathway, causing the inhibition of pro-inflammatory enzyme (iNOS and COX-2) and pro-inflammatory cytokine (TNF-α, IL-1β, and IL-6) production. Conclusions In conclusion, the present study supports the effectiveness of BHBA in protecting dopaminergic neurons against inflammatory challenge. |
| Related Links | https://jneuroinflammation.biomedcentral.com/counter/pdf/10.1186/s12974-014-0230-3.pdf |
| Ending Page | 14 |
| Page Count | 14 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 17422094 |
| DOI | 10.1186/s12974-014-0230-3 |
| Journal | Journal of Neuroinflammation |
| Issue Number | 1 |
| Volume Number | 12 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2015-01-17 |
| Access Restriction | Open |
| Subject Keyword | Neurosciences Neurology Neurobiology Immunology BHBA GPR109A Parkinson’s disease neuroinflammation LPS NF-κB |
| Content Type | Text |
| Resource Type | Article |
| Subject | Neuroscience Immunology Cellular and Molecular Neuroscience Neurology |
| Journal Impact Factor | 9.3/2023 |
| 5-Year Journal Impact Factor | 9.8/2023 |
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