Hypothyroidism Promotes Microglia M1 Polarization by Inhibiting BDNF-Promoted PI3K-Akt Signaling Pathway

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Introduction Hypothyroidism and its induced neurological-associated disorders greatly affect the health-related quality of patients' life. Meanwhile, microglia in brain have essential regulatory functions on neurodegeneration, but the underlying link between hypothyroidism and microglia function is largely ambiguous. Methods We deciphered how hypothyroidism modulates the polarization of microglia by constructing methimazole-induced mice model and checking the expression pattern of biomarkers of microglia M1 polarization. Then, we used lipopolysaccharide (LPS)-treated BV2 cells to explore the effecting factors on microglia M1 polarization. Finally, global transcriptome sequencing (RNA-seq) was utilized to identify the underlying regulatory mechanisms. Results We detected that biomarkers of microglia M1 polarization and pro-inflammatory cytokines were significantly increased in hypothyroidism mice brain; hypothyroidism could also repress the expression of BDNF and TrkB, and the anti-inflammatory cytokine such as IL-10. In BV2 cells, LPS treatment decreased expression of BDNF, IL-10, and Arg1, while BDNF overexpression (BDNF-OE) significantly reversed the inflammation induced by LPS. BDNF-OE significantly repressed expression of iNOS and TNF-α, but increased expression of IL-10 and Arg1. For mechanism, RNA-seq analysis demonstrated that BDNF-OE could globally regulate transcriptom

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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