Neurobiological Basis of Neuronal Survival

σ-1受体（Sig-1 R）作为与多种蛋白质和脂质相互作用的分子伴侣起作用，并且涉及神经退行性疾病和精神疾病。Sigma-1受体与Sp1信号转导有关。 本研究发现Sp1在星形胶质细胞中高表达，提示Sp1可能对星形胶质细胞的功能起重要作用。构建Sp1/GFAP-Cre-ERT 2条件性基因敲除小鼠，研究Sp1在星形胶质细胞中的作用。敲除星形胶质细胞中的Sp1改变了星形胶质细胞的形态，并降低了皮质和海马中GFAP的表达，但不影响细胞活力。星形胶质细胞中Sp1的缺失减少了皮质和海马中神经元的数量。Sp1基因敲除的原代星形胶质细胞的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Sp1基因敲除改变了基因表达，包括Toll样受体2和Cfb的表达减少，C1 q和C4 Bp的表达增加，从而影响神经突生长和突触形成，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脑损伤预防。

Sigma-1 receptor (Sig-1R) functions as a chaperon that interacts with multiple proteins and lipids and is implicated in neurodegenerative and psychiatric diseases. Sigma-1 receptor relates to Sp1 signaling. In this year, 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.