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Mol Neurobiol. 2020 Jan;57(1):261-277. doi: 10.1007/s12035-019-01694-7. Epub 2019 Jul 18.

Sp1 in Astrocyte Is Important for Neurite Outgrowth and Synaptogenesis.

Author information

1
Department of Biotechnology and Bioindustry Science, National Cheng-Kung University, Tainan, 701, Taiwan.
2
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
3
The PhD Program for Neural Regenerative Medicine, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.
4
Center for Neurotrauma and Neuroregeneration, Taipei Medical University, Taipei, Taiwan.
5
Cellular Pathobiology Section, Integrative Neuroscience Research Branch, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, MD, USA.
6
Department of Biotechnology and Bioindustry Science, National Cheng-Kung University, Tainan, 701, Taiwan. petehung@mail.ncku.edu.tw.
7
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan. petehung@mail.ncku.edu.tw.

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:

Astrocyte; Neurite outgrowth; Sp1; Synaptogenesis

PMID:
31317491
DOI:
10.1007/s12035-019-01694-7

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