Mental Health Center, Shantou University, Shantou, Guangdong, China; Department of Psychiatry, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
J Neurochem. 2014 Sep;130(6):780-9. doi: 10.1111/jnc.12771. Epub 2014 Jun 18.
Previous studies have demonstrated that quetiapine (QTP) may have neuroprotective properties; however, the underlying mechanisms have not been fully elucidated. In this study, we identified a novel mechanism by which QTP increased the synthesis of ATP in astrocytes and protected GABAergic neurons from aging-induced death. In 12-month-old mice, QTP significantly improved cell number of GABAegic neurons in the cortex and ameliorated anxiety-like behaviors compared to control group. Complimentary in vitro studies showed that QTP had no direct effect on the survival of aging GABAergic neurons in culture. Astrocyte-conditioned medium (ACM) pretreated with QTP (ACMQTP) for 24 h effectively protected GABAergic neurons against aging-induced spontaneous cell death. It was also found that QTP boosted the synthesis of ATP from cultured astrocytes after 24 h of treatment, which might be responsible for the protective effects on neurons. Consistent with the above findings, a Rhodamine 123 test showed that ACMQTP, not QTP itself, was able to prevent the decrease in mitochondrial membrane potential in the aging neurons. For the first time, our study has provided evidence that astrocytes may be the conduit through which QTP is able to exert its neuroprotective effects on GABAergic neurons. The neuroprotective properties of quetiapine (QTP) have not been fully understood. Here, we identify a novel mechanism by which QTP increases the synthesis of ATP in astrocytes and protects GABAergic neurons from aging-induced death in a primary cell culture model. In 12-month-old mice, QTP significantly improves cell number of GABAegic neurons and ameliorates anxiety-like behaviors. Our study indicates that astrocytes may be the conduit through which QTP exerts its neuroprotective effects on GABAergic neurons.
先前的研究表明喹硫平（QTP）可能具有神经保护特性；然而，其潜在机制尚未完全阐明。在这项研究中，我们确定了一种新的机制，即 QTP 增加星形胶质细胞中 ATP 的合成，并保护 GABA 能神经元免受衰老诱导的死亡。在 12 个月大的小鼠中，与对照组相比，QTP 显著增加了皮质中 GABA 能神经元的数量，并改善了焦虑样行为。补充的体外研究表明，QTP 对培养中的衰老 GABA 能神经元的存活没有直接影响。用 QTP 预处理星形胶质细胞条件培养基（ACMQTP）24 小时可有效保护 GABA 能神经元免受衰老诱导的自发性细胞死亡。还发现，QTP 在治疗 24 小时后可增强培养的星形胶质细胞中 ATP 的合成，这可能是神经元保护作用的原因。与上述发现一致，Rhodamine 123 试验表明，ACMQTP，而不是 QTP 本身，能够防止衰老神经元中线粒体膜电位的下降。我们的研究首次提供了证据，表明星形胶质细胞可能是 QTP 对 GABA 能神经元发挥神经保护作用的途径。喹硫平（QTP）的神经保护特性尚未完全理解。在这里，我们确定了一种新的机制，即 QTP 增加星形胶质细胞中 ATP 的合成，并在原代细胞培养模型中保护 GABA 能神经元免受衰老诱导的死亡。在 12 个月大的小鼠中，QTP 显著增加 GABA 能神经元的数量并改善焦虑样行为。我们的研究表明，星形胶质细胞可能是 QTP 对 GABA 能神经元发挥神经保护作用的途径。
