Department of Biotechnology and Bioindustry Science, National Cheng-Kung University, Tainan, 701, Taiwan.
Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Mol Neurobiol. 2020 Jan;57(1):261-277. doi: 10.1007/s12035-019-01694-7. Epub 2019 Jul 18.
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.
在这项研究中,我们发现 Sp1 在星形胶质细胞中高度表达,这表明 Sp1 可能对星形胶质细胞的功能很重要。我们构建了 Sp1/GFAP-Cre-ERT2 条件性敲除小鼠,以研究 Sp1 在星形胶质细胞中的作用。星形胶质细胞中的 Sp1 敲除改变了星形胶质细胞的形态,并降低了大脑皮层和海马体中的 GFAP 表达,但不影响细胞活力。星形胶质细胞中的 Sp1 缺失减少了大脑皮层和海马体中的神经元数量。Sp1 敲除的原代星形胶质细胞条件培养基破坏了神经元树突的生长和突触的形成,导致学习、记忆和运动行为异常。星形胶质细胞中的 Sp1 敲除改变了基因表达,包括降低 Toll 样受体 2 和 Cfb 的表达,增加 C1q 和 C4Bp 的表达,从而影响神经突的生长和突触的形成,导致神经元功能紊乱。研究这些基因调控可能有助于理解神经元发育和预防脑损伤。