Title |
TGF-β1 Neuroprotection via Inhibition of Microglial Activation in a Rat Model of Parkinson’s Disease
|
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Published in |
Journal of Neuroimmune Pharmacology, April 2017
|
DOI | 10.1007/s11481-017-9732-y |
Pubmed ID | |
Authors |
Xiao Chen, Zhan Liu, Bei-Bei Cao, Yi-Hua Qiu, Yu-Ping Peng |
Abstract |
Transforming growth factor (TGF)-β1 is a pleiotropic cytokine with immunosuppressive and anti-inflammatory properties. Recently we have shown that TGF-β1 pretreatment in vitro protects against 1-methyl-4-phenylpyridinium (MPP(+))-induced dopaminergic neuronal loss that characterizes in Parkinson's disease (PD). Herein, we aimed to demonstrate that TGF-β1 administration in vivo after MPP(+) toxicity has neuroprotection that is achieved by a mediation of microglia. A rat model of PD was prepared by injecting MPP(+) unilaterally in the striatum. At 14 days after MPP(+) injection, TGF-β1 was administrated in the right lateral cerebral ventricle. Primary ventral mesencephalic (VM) neurons and cerebral cortical microglia were treated by MPP(+), respectively, and TGF-β1 was applied to neuronal or microglial cultures at 1 h after MPP(+) treatment. As expected, MPP(+) resulted in decrease in TGF-β1 production in the substantia nigra and in primary VM neurons and microglia. TGF-β1 intracerebroventricular administration alleviated MPP(+)-induced PD-like changes in pathology, motor coordination and behavior. Meanwhile, TGF-β1 ameliorated MPP(+)-induced microglial activation and inflammatory cytokine production in vivo. Interestingly, TGF-β1 treatment was not able to ameliorate MPP(+)-induced dopaminergic neuronal loss and caspase-3/9 activation in mono-neuron cultures, but TGF-β1 alleviated MPP(+)-induced microglial activation and inflammatory cytokine production in microglia-enriched cultures. This effect of TGF-β1 inhibiting microglial inflammatory response was blocked by Smad3 inhibitor SIS3. Importantly, neuronal exposure to supernatants of primary microglia that had been treated with TGF-β1 reduced dopaminergic neuronal loss and caspase-3/9 activation induced by MPP(+)-treated microglial supernatants. These findings establish that TGF-β1 exerts neuroprotective property in PD by inhibiting microglial inflammatory response via Smad3 signaling. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 38 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Bachelor | 9 | 24% |
Student > Ph. D. Student | 9 | 24% |
Student > Master | 4 | 11% |
Other | 3 | 8% |
Professor | 2 | 5% |
Other | 5 | 13% |
Unknown | 6 | 16% |
Readers by discipline | Count | As % |
---|---|---|
Neuroscience | 11 | 29% |
Biochemistry, Genetics and Molecular Biology | 5 | 13% |
Agricultural and Biological Sciences | 5 | 13% |
Medicine and Dentistry | 5 | 13% |
Immunology and Microbiology | 4 | 11% |
Other | 3 | 8% |
Unknown | 5 | 13% |