Sp1 in Astrocyte Is Important for Neurite Outgrowth and Synaptogenesis

被引:20
作者
Hung, Chia-Yang [1 ,2 ]
Hsu, Tsung-, I [2 ,3 ]
Chuang, Jian-Ying [3 ,4 ]
Su, Tsung-Ping [5 ]
Chang, Wen-Chang [2 ]
Hung, Jan-Jong [1 ,2 ]
机构
[1] Natl Cheng Kung Univ, Dept Biotechnol & Bioind Sci, Tainan 701, Taiwan
[2] Taipei Med Univ, Grad Inst Med Sci, Coll Med, Taipei, Taiwan
[3] Taipei Med Univ, Coll Med Sci & Technol, PhD Program Neural Regenerat Med, Taipei, Taiwan
[4] Taipei Med Univ, Ctr Neurotrauma & Neuroregenerat, Taipei, Taiwan
[5] NIDA, Cellular Pathobiol Sect, Integrat Neurosci Res Branch, NIH,US Dept HHS, Baltimore, MD USA
关键词
Sp1; Astrocyte; Neurite outgrowth; Synaptogenesis; TRANSCRIPTION FACTOR SP4; TOLL-LIKE RECEPTORS; NF-KAPPA-B; GENE; ACTIVATION; EXPRESSION; PROTEIN; COMPLEMENT; GROWTH; ASSOCIATION;
D O I
10.1007/s12035-019-01694-7
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
In this study, we found that Sp1 was highly expressed in astrocytes, implying that Sp1 might be important for the function of astrocytes. Sp1/GFAP-Cre-ERT2 conditional knockout mice were constructed to study the role of Sp1 in astrocytes. Knockout of Sp1 in astrocytes altered astrocytic morphology and decreased GFAP expression in the cortex and hippocampus but did not affect cell viability. Loss of Sp1 in astrocytes decreased the number of neurons in the cortex and hippocampus. Conditioned medium from primary astrocytes with Sp1 knockout disrupted neuronal dendritic outgrowth and synapse formation, resulting in abnormal learning, memory, and motor behavior. Sp1 knockout in astrocytes altered gene expression, including decreasing the expression of Toll-like receptor 2 and Cfb and increasing the expression of C1q and C4Bp, thereby affecting neurite outgrowth and synapse formation, resulting in disordered neuron function. Studying these gene regulations might be beneficial to understanding neuronal development and brain injury prevention.
引用
收藏
页码:261 / 277
页数:17
相关论文
共 53 条
[1]   Cell Biology of Astrocyte-Synapse Interactions [J].
Allen, Nicola J. ;
Eroglu, Cagla .
NEURON, 2017, 96 (03) :697-708
[2]   Histone Modifiers, YY1 and p300, Regulate the Expression of Cartilage-specific Gene, Chondromodulin-I, in Mesenchymal Stem Cells [J].
Aoyama, Tomoki ;
Okamoto, Takeshi ;
Fukiage, Kenichi ;
Otsuka, Seiji ;
Furu, Moritoshi ;
Ito, Kinya ;
Jin, Yonghui ;
Ueda, Michiko ;
Nagayama, Satoshi ;
Nakayama, Tomitaka ;
Nakamura, Takashi ;
Toguchida, Junya .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2010, 285 (39) :29842-29850
[3]   Cooperation of Spl and p300 in the induction of the CDK inhibitor p21WAF1/CIP1 during NGF-mediated neuronal differentiation [J].
Billon, N ;
Carlisi, D ;
Datto, MB ;
van Grunsven, LA ;
Watt, A ;
Wang, XF ;
Rudkin, BB .
ONCOGENE, 1999, 18 (18) :2872-2882
[4]   Immune Proteins in Brain Development and Synaptic Plasticity [J].
Boulanger, Lisa M. .
NEURON, 2009, 64 (01) :93-109
[5]   Sp3 and sp4 transcription factor levels are increased in brains of patients with Alzheimer's disease [J].
Boutillier, Stephanie ;
Lannes, Beatricel ;
Buee, Luc ;
Dlelacourte, Andre ;
Rouaux, Caroline ;
Mohr, Michel ;
Bellocq, Jean-Pierre ;
Sellal, Francois ;
Larmet, Yves ;
Boutillier, Anne-Laurence ;
Loeffler, Jean-Philippe .
NEURODEGENERATIVE DISEASES, 2007, 4 (06) :413-423
[6]   Human Astrocytes: Secretome Profiles of Cytokines and Chemokines [J].
Choi, Sung S. ;
Lee, Hong J. ;
Lim, Inja ;
Satoh, Jun-ichi ;
Kim, Seung U. .
PLOS ONE, 2014, 9 (04)
[7]   Specificity protein 1-zinc finger protein 179 pathway is involved in the attenuation of oxidative stress following brain injury [J].
Chuang, Jian-Ying ;
Kao, Tzu-Jen ;
Lin, Shu-Hui ;
Wu, An-Chih ;
Lee, Pin-Tse ;
Su, Tsung-Ping ;
Yeh, Shiu-Hwa ;
Lee, Yi-Chao ;
Wu, Chung-Che ;
Chang, Wen-Chang .
REDOX BIOLOGY, 2017, 11 :135-143
[8]   Astrocytes Control Synapse Formation, Function, and Elimination [J].
Chung, Won-Suk ;
Allen, Nicola J. ;
Eroglu, Cagla .
COLD SPRING HARBOR PERSPECTIVES IN BIOLOGY, 2015, 7 (09)
[9]  
Citron Bruce A, 2015, Am J Neurodegener Dis, V4, P40
[10]   Regulation of synaptic connectivity by glia [J].
Eroglu, Cagla ;
Barres, Ben A. .
NATURE, 2010, 468 (7321) :223-231