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Sp1 in Astrocyte Is Important for Neurite Outgrowth and Synaptogenesis

  • Chia-Yang Hung
  • Tsung-I Hsu
  • Jian-Ying Chuang
  • Tsung-Ping Su
  • Wen-Chang Chang
  • Jan-Jong HungEmail author
Article

Abstract

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.

Keywords

Sp1 Astrocyte Neurite outgrowth Synaptogenesis 

Notes

Acknowledgments

We are grateful for the support of clinical specimens from the Human Biobank, Research Center of Clinical Medicine, and National Cheng Kung University Hospital.

Funding Information

This work was supported by the grants (106-2320-B-006-065-MY3, 106-2320-B-006-020-MY3, and 104-2923-B-038-002-MY3) obtained from the Ministry of Science and Technology, Taiwan.

Supplementary material

12035_2019_1694_MOESM1_ESM.jpg (468 kb)
Supplementary figure 1 Sp1 expression level in Sp1 knockout mice. Wild type, Sp1f/+ and Sp1f/f mice were treated with tamoxifen and then sacrificed. The Sp1 level was studied by Western blot with anti-Sp1 antibodies. The Sp1 level was quantified and statistical assay by t-test, *<0.05, **<0.01. (JPG 467 kb)
12035_2019_1694_MOESM2_ESM.jpg (760 kb)
Supplementary figure 2 Sp1-mediated pathway and molecular function in astrocyte. Sp1 was knockout from astrocyte by tamoxifen treatment, and then the RNA was isolated for performing the cDNA array. The gene expression involved in pathways (A) and molecular function (B) was analysis by Gene Ontology analysis. (JPG 760 kb)
12035_2019_1694_MOESM3_ESM.jpg (1 mb)
Supplementary figure 3 Sp1 in astrocyte regulates the pathways and various biological processes in neurons. Conditional medium was collected from wild type astrocyte or Sp1 knockout astrocyte, and then treated the neurons. The RNA was isolated for performing the cDNA array. The gene expression involved in pathways (A) and biological processes (B) was analysis by Gene Ontology analysis. (JPG 1038 kb)
12035_2019_1694_MOESM4_ESM.jpg (1 mb)
Supplementary figure 4 Sp1 in astrocyte regulates the group of proteins in neurons. The proteomic clusters was analyzed in neuron treated with conditional medium from astrocytes with or without Sp1 knockout. (JPG 1042 kb)

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Authors and Affiliations

  1. 1.Department of Biotechnology and Bioindustry ScienceNational Cheng-Kung UniversityTainanTaiwan
  2. 2.Graduate Institute of Medical Sciences, College of MedicineTaipei Medical UniversityTaipeiTaiwan
  3. 3.The PhD Program for Neural Regenerative Medicine, College of Medical Science and TechnologyTaipei Medical UniversityTaipeiTaiwan
  4. 4.Center for Neurotrauma and NeuroregenerationTaipei Medical UniversityTaipeiTaiwan
  5. 5.Cellular Pathobiology Section, Integrative Neuroscience Research Branch, National Institute on Drug Abuse, National Institutes of HealthDepartment of Health and Human ServicesBaltimoreUSA

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