Abstract：
Repeated exposure to propofol during early brain development is associated with anxiety disorders in adulthood, yet the mechanisms underlying propofol-induced susceptibility to anxiety disorders remain elusive. The lateral septum (LS), primarily composed of γ-aminobutyric acidergic (GABAergic) neurons, serves as a key brain region in the regulation of anxiety. However, it remains unclear whether LS GABAergic neurons are implicated in propofol-induced anxiety. Therefore, we conducted c-Fos immunostaining of whole-brain slices from mice exposed to propofol during early life. Our findings indicate that propofol exposure activates GABAergic neurons in the LS. Selective activation of LS GABAergic neurons resulted in increased anxiety-like behavior, while selective inhibition of these neurons reduced such behaviors. These results suggest that the LS is a critical brain region involved in propofol-induced anxiety. Furthermore, we investigated the molecular mechanism of propofol-induced anxiety in the LS. Microglia activation underlies the development of anxiety. Immunofluorescence staining and Western blot analysis of LS revealed activated microglia and significantly elevated levels of phospho-NF-κB p65 protein. Additionally, a decrease in the number of neuronal spines was observed. Our study highlights the crucial role of the LS in the development of anxiety-like behavior in adulthood following childhood propofol exposure, accompanied by the activation of inflammatory pathways.
摘要：
在早期大脑发育过程中反复接触异丙酚与成年期焦虑症有关，然而,异丙酚诱发焦虑障碍易感性的潜在机制仍然难以捉摸.侧隔（LS），主要由γ-氨基丁酸能（GABA能）神经元组成，作为调节焦虑的关键大脑区域。然而,目前尚不清楚LSGABA能神经元是否与异丙酚诱导的焦虑有关.因此,我们对早期暴露于丙泊酚的小鼠的全脑切片进行了c-Fos免疫染色.我们的发现表明异丙酚暴露会激活LS中的GABA能神经元。LSGABA能神经元的选择性激活导致焦虑样行为增加，而对这些神经元的选择性抑制减少了这种行为。这些结果表明，LS是涉及异丙酚引起的焦虑的关键大脑区域。此外，我们研究了LS中丙泊酚诱导焦虑的分子机制。小胶质细胞激活是焦虑发展的基础。LS的免疫荧光染色和Western印迹分析显示小胶质细胞活化，磷酸化NF-κBp65蛋白水平显着升高。此外,观察到神经元棘的数量减少。我们的研究强调了LS在儿童丙泊酚暴露后成年期焦虑样行为发展中的关键作用，伴随着炎症途径的激活。
