Correlations between omega-3 fatty acids and inflammatory/glial abnormalities: the involvement of the membrane and neurotransmitter dysfunction in schizophrenia

Yongping Zhang; Jingwen Yin; Haifeng Yan; Ling Yan; Yuyu Li; Cai Zhang; Yajuan Li; Baiping Liu; Juda Lin; Liqiang Zhang; Xueqiong Hu; Cai Song

doi:10.3389/fncel.2023.1163764

Correlations between omega-3 fatty acids and inflammatory/glial abnormalities: the involvement of the membrane and neurotransmitter dysfunction in schizophrenia

Front Cell Neurosci. 2023 Oct 23:17:1163764. doi: 10.3389/fncel.2023.1163764. eCollection 2023.

Authors

Yongping Zhang^#^{1

2

3}, Jingwen Yin^#⁴, Haifeng Yan⁴, Ling Yan¹, Yuyu Li¹, Cai Zhang¹, Yajuan Li¹, Baiping Liu¹, Juda Lin⁴, Liqiang Zhang⁵, Xueqiong Hu¹, Cai Song^{1

2

3}

Affiliations

¹ Research Institute for Marine Drugs and Nutrition, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang, China.
² Marine Medicine Research and Development Center of Shenzhen Institutes of Guangdong Ocean University, Shenzhen, China.
³ Guangdong Provincial Key Laboratory of Aquatic Product Processing and Safety, College of Food Science and Technology, Guangdong Ocean University, Zhanjiang, China.
⁴ Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.
⁵ Zhanjiang Third People's Hospital, Zhanjiang, China.

^# Contributed equally.

Abstract

Introduction: 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.

Methods: Changes in T-helper (h) patterns, peripheral macrophage/glial markers, PUFAs profile, membrane fluidity, and neurotransmitter functions were evaluated in SZ patients (n = 50) and healthy controls (n = 30) using ELISA, gas chromatography, fluorescence anisotropy techniques, and HPLC, respectively.

Results: 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.

Discussion: 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.

Keywords: cytokines; inflammation; neurotransmitters; polyunsaturated fatty acids (PUFAs); schizophrenia (SZ).

Grants and funding

This study was supported by the Natural Science Foundation of Guangdong Province (2021A1515011579), the Shenzhen Science and Technology Plan (International Cooperation Research) Project (GJHZ20190823111414825), the Zhanjiang Science and Technology Project (2021A05046), the Project of Innovation training for College Students (010403042123), and the Research Start-Up Funds of Guangdong Ocean University (R19038).