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

1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

Beyond Hormone Levels: Thyroid Hormone Signaling from Neurogenesis to Alzheimer's Disease.Cells · 2026
Review
Plant-derived nutritional components in thyroid disease-related neuropsychiatric disorders: mechanistic insights and advances.Frontiers in nutrition · 2026
Review
The Role of Traditional Chinese Medicine in Metabolic Reprogramming, Tumor microenvironment, and Macrophage Regulation: Mechanisms and Advances in Preclinical Studies.Journal of Cancer · 2026
Review
Magnesium L-Threonate Reduces Hippocampal Amyloid-β Load without Cognitive Improvement in a PTU-induced Hypothyroidism Model in Young Rats.Molecular neurobiology · 2025
Article
Nuclear receptors in metabolic, inflammatory, and oncologic diseases: mechanisms, therapeutic advances, and future directions.European journal of medical research · 2025
Review

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Yuan ZhanDepartment of Geriatric Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, China, zzhan192623@126.com.

Lang LangDepartment of Geriatric Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

Fen WangDepartment of Geriatric Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

Xian WuThe Key Laboratory of Anti-Inflammatory and Immune Medicines, Anhui Medical University, Ministry of Education, Hefei, China.

Haiwang ZhangThe Key Laboratory of Anti-Inflammatory and Immune Medicines, Anhui Medical University, Ministry of Education, Hefei, China.

Yuelin DongThe Key Laboratory of Anti-Inflammatory and Immune Medicines, Anhui Medical University, Ministry of Education, Hefei, China.

Hao YangDepartment of Geriatric Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

Defa ZhuDepartment of Geriatric Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionHypothyroidism 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.

methodsWe 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.

resultsWe 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 transcriptome profile by affecting gene expression. In LPS-treated BV2 cells, BDNF-OE significantly altered expression pattern of genes involved in PI3K-Akt signaling pathway, including Thbs3, Myc, Gdnf, Thbs1, and Ccnd1 as upregulated genes, and Gnb4, Fgf22, Pik3r3, Pgf, Cdkn1a, and Pdgfra as downregulated genes. Myc, Gdnf, Thbs1, and Ccnd1 showed much higher expression levels than other genes in PI3K-Akt signaling pathway and could be promising targets of BDNF in reversing microglia M1 polarization.

conclusionOur study demonstrated a sound conclusion that hypothyroidism promotes microglia M1 polarization by inhibiting BDNF expression in brain; BDNF could inhibit the M1 polarization of microglia by activating PI3K-Akt signaling pathway, which could serve as a promising therapeutic target for microglia-induced neurodegenerative or emotional disorders in future.

introductionHypothyroidism 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.

methodsWe 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.

resultsWe 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 transcriptome profile by affecting gene expression. In LPS-treated BV2 cells, BDNF-OE significantly altered expression pattern of genes involved in PI3K-Akt signaling pathway, including Thbs3, Myc, Gdnf, Thbs1, and Ccnd1 as upregulated genes, and Gnb4, Fgf22, Pik3r3, Pgf, Cdkn1a, and Pdgfra as downregulated genes. Myc, Gdnf, Thbs1, and Ccnd1 showed much higher expression levels than other genes in PI3K-Akt signaling pathway and could be promising targets of BDNF in reversing microglia M1 polarization.

conclusionOur study demonstrated a sound conclusion that hypothyroidism promotes microglia M1 polarization by inhibiting BDNF expression in brain; BDNF could inhibit the M1 polarization of microglia by activating PI3K-Akt signaling pathway, which could serve as a promising therapeutic target for microglia-induced neurodegenerative or emotional disorders in future.

Indexed as

Brain-Derived Neurotrophic FactorHypothyroidismMicrogliaPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktAnimalsLipopolysaccharidesMaleMiceMice, Inbred C57BLSignal TransductionBdnf protein, mouseBrain-Derived Neurotrophic FactorLipopolysaccharidesPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktBDNFHypothyroidismMicroglia M1 polarizationPhosphoinositide 3 kinase-Akt signaling pathwayRNA-seq