Zhang Yongping, Yin Jingwen, Yan Haifeng, Yan Ling, Li Yuyu, Zhang Cai, Li Yajuan, Liu Baiping, Lin Juda, Zhang Liqiang, Hu Xueqiong, Song Cai
Research Institute for Marine Drugs and Nutrition, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang, China.
Marine Medicine Research and Development Center of Shenzhen Institutes of Guangdong Ocean University, Shenzhen, China.
Front Cell Neurosci. 2023 Oct 23;17:1163764. doi: 10.3389/fncel.2023.1163764. eCollection 2023.
Macrophages or T-lymphocytes triggered inflammation and, consequently, activated glial cells may contribute to neuroinflammation and neurotransmitter dysfunction in schizophrenia (SZ), while omega(n)-3 polyunsaturated fatty acids (PUFAs) can attenuate some SZ symptoms through anti-inflammatory effects. However, the correlations between macrophage/T-lymphocyte-produced cytokines and glia phenotypes, between inflammatory status and PUFAs composition, between cytokines and neurotransmitter function, and between n-3 PUFAs and neurotransmitter abnormality in SZ are unclear.
Changes in T-helper (h) patterns, peripheral macrophage/glial markers, PUFAs profile, membrane fluidity, and neurotransmitter functions were evaluated in SZ patients ( = 50) and healthy controls ( = 30) using ELISA, gas chromatography, fluorescence anisotropy techniques, and HPLC, respectively.
Compared to the control, blood lymphocyte proliferation, the concentration of macrophage/microglia phenotype M1 markers, including cytokines IL-1β, TNF-α (Th1) and IL-6 (Th2), and astrocyte phenotype A1 marker S100β was significantly increased, while IL-17 and n-3 PUFAs contents, n-3/n-6 ratio, and membrane fluidity (FLU) were significantly decreased in SZ. Moreover, increased DA and HVA, decreased 5-HT and NE, and their metabolites appeared in SZ. Moreover, negative correlations between IL-6 and A2 marker Brain-Derived Neurotrophic Factor (BDNF) or n-3 PUFAs EPA and between IL-1β and FLU or 5HIAA, while positive correlations between EPA and 5-HIAA and between FLU and DHA were found in SZ.
These findings showed (1) no clear Th pattern, but pro-inflammatory-dominant immunity occurred; (2) the pro-inflammatory pattern may result in the activated microglia M1 and astrocyte A1 phenotype; and (3) increased pro-inflammatory cytokines were related to decreased n-3 PUFA and decreased membrane fluidity and dysfunctional neurotransmitter systems in SZ.
巨噬细胞或T淋巴细胞引发炎症，进而激活的神经胶质细胞可能导致精神分裂症（SZ）中的神经炎症和神经递质功能障碍，而ω-3多不饱和脂肪酸（PUFAs）可通过抗炎作用减轻一些SZ症状。然而，SZ中巨噬细胞/T淋巴细胞产生的细胞因子与神经胶质细胞表型之间、炎症状态与PUFAs组成之间、细胞因子与神经递质功能之间以及n-3 PUFAs与神经递质异常之间的相关性尚不清楚。
分别使用酶联免疫吸附测定（ELISA）、气相色谱法、荧光各向异性技术和高效液相色谱法（HPLC）评估了SZ患者（n = 50）和健康对照者（n = 30）中辅助性T（h）模式、外周巨噬细胞/神经胶质细胞标志物、PUFAs谱、膜流动性和神经递质功能的变化。
与对照组相比，SZ患者的血液淋巴细胞增殖、巨噬细胞/小胶质细胞表型M1标志物的浓度显著增加，包括细胞因子白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α，Th1型）和白细胞介素-6（IL-6，Th2型），以及星形胶质细胞表型A1标志物S100β；而IL-17和n-3 PUFAs含量、n-3/n-6比值和膜流动性（FLU）显著降低。此外，SZ患者出现多巴胺（DA）和高香草酸（HVA）增加、5-羟色胺（5-HT）和去甲肾上腺素（NE）及其代谢产物减少的情况。此外，在SZ患者中发现IL-6与A2标志物脑源性神经营养因子（BDNF）或n-3 PUFAs二十碳五烯酸（EPA）之间、IL-1β与FLU或5-羟吲哚乙酸（5HIAA）之间呈负相关，而EPA与5-HIAA之间以及FLU与二十二碳六烯酸（DHA）之间呈正相关。
这些发现表明：（1）没有明确的Th模式，但出现了以促炎为主的免疫反应；（2）促炎模式可能导致小胶质细胞M1和星形胶质细胞A1表型激活；（3）促炎细胞因子增加与SZ患者中n-3 PUFA减少、膜流动性降低和神经递质系统功能障碍有关。
