Department of Psychoimmunology, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
Department of Neuropsychiatry, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan.
Biomed Res Int. 2021 Oct 18;2021:9975865. doi: 10.1155/2021/9975865. eCollection 2021.
Interleukin-18 (IL-18) is an inflammatory cytokine that has been linked to energy homeostasis and psychiatric symptoms such as depression and cognitive impairment. We previously revealed that deficiency in IL-18 led to hippocampal abnormalities and resulted in depression-like symptoms. However, the impact of IL-18 deficiency on other brain regions remains to be clarified. In this study, we first sought to confirm that IL-18 expression in neural cells can be found in human brain tissue. Subsequently, we examined the expression of genes in the prefrontal cortex of mice and compared it with gene expression in mice subjected to a chronic mild stress model of depression. Extracted genes were further analyzed using Ingenuity® Pathway Analysis, in which 18 genes common to both the chronic mild stressed model and mice were identified. Of those, 16 were significantly differentially expressed between and mice. We additionally measured protein expression of -2-HS-glycoprotein (AHSG) and transthyretin (TTR) in serum and the brain. In the prefrontal cortex of mice, TTR but not AHSG was significantly decreased. Conversely, in the serum of mice, AHSG was significantly increased but not TTR. Therefore, our results suggest that in IL-18-deficit conditions, TTR in the brain is one of the mediators causally related to depression, and AHSG in peripheral organs is one of the regulators inducing energy imbalance. Moreover, this study suggests a possible "signpost" to clarify the molecular mechanisms commonly underlying the immune system, energy metabolism, neural function, and depressive disorders.
白细胞介素-18（IL-18）是一种炎症细胞因子，与能量稳态和精神症状（如抑郁和认知障碍）有关。我们之前的研究表明，IL-18 缺乏会导致海马体异常，并导致类似抑郁的症状。然而，IL-18 缺乏对其他脑区的影响仍有待阐明。在这项研究中，我们首先试图证实人类脑组织中存在神经细胞中的 IL-18 表达。随后，我们检查了小鼠前额叶皮层中的基因表达，并将其与抑郁的慢性轻度应激模型小鼠中的基因表达进行了比较。使用 Ingenuity® Pathway Analysis 进一步分析提取的基因，确定了慢性轻度应激模型和 IL-18 缺陷型小鼠共有的 18 个基因。其中，16 个基因在 和 小鼠之间的表达差异显著。我们还测量了血清和大脑中 -2-HS-糖蛋白（AHSG）和转甲状腺素（TTR）的蛋白表达。在 IL-18 缺陷型小鼠的前额叶皮层中，TTR 而非 AHSG 显著减少。相反，在 IL-18 缺陷型小鼠的血清中，AHSG 显著增加而 TTR 没有增加。因此，我们的结果表明，在 IL-18 缺乏的情况下，大脑中的 TTR 是与抑郁有因果关系的介质之一，而外周器官中的 AHSG 是导致能量失衡的调节因子之一。此外，这项研究为阐明免疫系统、能量代谢、神经功能和抑郁障碍的共同分子机制提供了一个可能的“信号”。
