Minocycline reduces neuroinflammation but does not ameliorate neuron loss in a mouse model of neurodegeneration

被引:56
作者
Cheng, Shanshan [1 ]
Hou, Jinxing [2 ]
Zhang, Chen [1 ]
Xu, Congyu [1 ]
Wang, Long [1 ]
Zou, Xiaoxia [1 ]
Yu, Huahong [2 ]
Shi, Yun [1 ]
Yin, Zhenyu [3 ]
Chen, Guiquan [1 ]
机构
[1] Nanjing Univ, MOE Key Lab Model Anim Dis Study, Model Anim Res Ctr, Nanjing 210061, Jiangsu, Peoples R China
[2] Nanchang Univ, Sch Life Sci, Nanchang 330031, Jiangxi, Peoples R China
[3] Nanjing Univ, Sch Med, Nanjing Drum Tower Hosp, Dept Geriatr, Nanjing 210008, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
AMYOTROPHIC-LATERAL-SCLEROSIS; ALZHEIMERS-DISEASE; MICROGLIAL ACTIVATION; ENZYME DICER; CELL-DEATH; EXPRESSION; PROTEIN; KNOCKOUT; MEMORY; IMPAIRMENT;
D O I
10.1038/srep10535
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];
摘要
Minocycline is a broad-spectrum tetracycline antibiotic. A number of preclinical studies have shown that minocycline exhibits neuroprotective effects in various animal models of neurological diseases. However, it remained unknown whether minocycline is effective to prevent neuron loss. To systematically evaluate its effects, minocycline was used to treat Dicer conditional knockout (cKO) mice which display age-related neuron loss. The drug was given to mutant mice prior to the occurrence of neuroinflammation and neurodegeneration, and the treatment had lasted 2 months. Levels of inflammation markers, including glial fibrillary acidic protein (GFAP), ionized calcium-binding adapter molecule1 (Iba1) and interleukin6 (IL6), were significantly reduced in minocycline-treated Dicer cKO mice. In contrast, levels of neuronal markers and the total number of apoptotic cells in Dicer cKO mice were not affected by the drug. In summary, inhibition of neuroinflammation by minocycline is insufficient to prevent neuron loss and apoptosis.
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页数:14
相关论文
共 60 条
[1]
CREB Binding Protein Is Required for Both Short-Term and Long-Term Memory Formation [J].
Chen, Guiquan ;
Zou, Xiaoyan ;
Watanabe, Hirotaka ;
van Deursen, Jan M. ;
Shen, Jie .
JOURNAL OF NEUROSCIENCE, 2010, 30 (39) :13066-13077
[2]
Minocycline inhibits caspase-1 and caspase-3 expression and delays mortality in a transgenic mouse model of Huntington disease [J].
Chen, M ;
Ona, VO ;
Li, MW ;
Ferrante, RJ ;
Fink, KB ;
Zhu, S ;
Bian, J ;
Guo, L ;
Farrell, LA ;
Hersch, SM ;
Hobbs, W ;
Vonsattel, JP ;
Cha, JHJ ;
Friedlander, RM .
NATURE MEDICINE, 2000, 6 (07) :797-+
[3]
Age-dependent neuron loss is associated with impaired adult neurogenesis in forebrain neuron-specific Dicer conditional knockout mice [J].
Cheng, Shanshan ;
Zhang, Chen ;
Xu, Congyu ;
Wang, Long ;
Zou, Xiaoxia ;
Chen, Guiquan .
INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY, 2014, 57 :186-196
[4]
Minocycline attenuates neuronal cell death and improves cognitive impairment in Alzheimer's Disease models [J].
Choi, Yoori ;
Kim, Hye-Sun ;
Shin, Ki Young ;
Kim, Eun-Mee ;
Kim, Minji ;
Kim, Hyun-Soo ;
Park, Cheol Hyoung ;
Jeong, Yun Ha ;
Yoo, Jongman ;
Lee, Jean-Pyo ;
Chang, Keun-A ;
Kim, Seonghan ;
Suh, Yoo-Hun .
NEUROPSYCHOPHARMACOLOGY, 2007, 32 (11) :2393-2404
[5]
Conditional loss of Dicer disrupts cellular and tissue morphogenesis in the cortex and hippocampus [J].
Davis, Tigwa H. ;
Cuellar, Trinna L. ;
Koch, Selina M. ;
Barker, Allison J. ;
Harfe, Brian D. ;
McManus, Michael T. ;
Ullian, Erik M. .
JOURNAL OF NEUROSCIENCE, 2008, 28 (17) :4322-4330
[6]
Delay C, 2011, INT J ALZHEIMERS DIS, V2011
[7]
MicroRNAs in Alzheimer's disease [J].
Delay, Charlotte ;
Mandemakers, Wim ;
Hebert, Sebastien S. .
NEUROBIOLOGY OF DISEASE, 2012, 46 (02) :285-290
[8]
MICROGLIA AND CYTOKINES IN NEUROLOGICAL DISEASE, WITH SPECIAL REFERENCE TO AIDS AND ALZHEIMERS-DISEASE [J].
DICKSON, DW ;
LEE, SC ;
MATTIACE, LA ;
YEN, SHC ;
BROSNAN, C .
GLIA, 1993, 7 (01) :75-83
[9]
Minocycline reduces microglial activation and improves behavioral deficits in a transgenic model of cerebral microvascular amyloid [J].
Fan, Rong ;
Xu, Feng ;
Previti, Mary Lou ;
Davis, Judianne ;
Grande, Alicia M. ;
Robinson, John K. ;
Van Nostrand, William E. .
JOURNAL OF NEUROSCIENCE, 2007, 27 (12) :3057-3063
[10]
Forebrain degeneration and ventricle enlargement caused by double knockout of Alzheimer's presenilin-1 and presenilin-2 [J].
Feng, RB ;
Wang, HM ;
Wang, JL ;
Shrom, D ;
Zeng, XM ;
Tsien, JZ .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (21) :8162-8167