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Lipopolysaccharide potentiates dopaminergic neuronal dysfunction in α-synuclein transgenic mice
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Yuan-peng ZHENG, Cai-xia ZANG, Lu WANG, Han-yu YANG, Hua SUN, Xiu-qi BAO*, Dan ZHANG*
Acta Pharmaceutica Sinica | 2017, 52(5) : 729 - 736
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Acta Pharmaceutica Sinica | 2017, 52(5): 729-736
ORIGINAL ARTICLES Pharmacology
Lipopolysaccharide potentiates dopaminergic neuronal dysfunction in α-synuclein transgenic mice
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Yuan-peng ZHENG, Cai-xia ZANG, Lu WANG, Han-yu YANG, Hua SUN, Xiu-qi BAO*, Dan ZHANG*
Affiliations
  • State Key Laboratory of Natural Products and Functions, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
Published: 2017-05-12 doi: 10.16438/j.0513-4870.2017-0065
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Parkinson's disease (PD) is the most prevalent neurodegenerative disorder, with several risk factors contributing to the onset, such as aging, genetics, oxidative stress and neuroinflammation. There are several PD animals that mimics different risk factor. α-Synuclein mutation mice and systemic lipopolysaccharide (LPS) injection mice are two kinds of most common animal models that replicate genetic mutation and neuroinflammation, respectively. However, in these two animal models, the pathogenesis occurred after a long period of stimulation. In the present study, four-month-old α-synucleintransgenic mice (A53T) were intraperitoneally injected with LPS once a week for continuous 8 weeks to simulate the inflammatory response. The behavioral results showed that the time of mice staying on the rod and the performance score were markedly decreased, indicating motor dysfunction. Dopaminergic neuronal function also decreased. It was noted that the movement dysfunction and pathological changes were aggravated in LPS plus α-synuclein challenged mice compared with LPS or α-synuclein stimulated alone, suggesting that the double attack had synergistic effects. Mechanistic study demonstrated that LPS and α-synuclein combined challenge led to obvious neuroinflammatory response and apoptosis, which might contribute to motor and dopaminergic neuronal dysfunction. In addition, differential proteomic study showed that the expression of CD99L2 and COX7RP significantly increased in the midbrain of LPS plus α-synuclein challenged mice, which were closely related to inflammation and apoptosis, and might be involved in the pathogenesis of PD. In conclusion, the present study demonstrated that LPS could potentiate dopaminergic neuronal function in α-synuclein transgenic mice, which might be an ideal method to develop PD animal model.

Parkinson's disease  /  lipopolysaccharide  /  α-synuclein  /  neuroinflammation
Yuan-peng ZHENG, Cai-xia ZANG, Lu WANG, Han-yu YANG, Hua SUN, Xiu-qi BAO, Dan ZHANG. Lipopolysaccharide potentiates dopaminergic neuronal dysfunction in α-synuclein transgenic mice[J]. Acta Pharmaceutica Sinica, 2017 , 52 (5) : 729 -736 . DOI: 10.16438/j.0513-4870.2017-0065
Year 2017 volume 52 Issue 5
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doi: 10.16438/j.0513-4870.2017-0065
  • Receive Date:2017-01-16
  • Online Date:2026-01-14
  • Published:2017-05-12
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  • Received:2017-01-16
  • Revised:2017-03-08
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    State Key Laboratory of Natural Products and Functions, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
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表12种不同金属材料的力学参数

Family
属数
Number of
genus
种数
Number of
species
占总种数比例
Percentage of
total species (%)

Genus
种数
Number of
species
占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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