Evidence map›Paper›PMID 39905477›Full record

ArticleBiology of sex differences2025

Sex differences in the neuroinflammatory signaling pathway: effect of miRNAs on fatty acid synthesis in microglia.

Haolin Zheng, Akiko Mizokami, Sergio Romera-Giner, Jaime Llera-Oyola, Yosuke Yamawaki, Tomomi Sano, Eijiro Jimi, Francisco García-García, Takashi Kanematsu

Abstract read
In one paragraph

Article in Biology of sex differences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Article
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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

9 authors.

Haolin Zheng *Department of Cell Biology, Aging Science, and Pharmacology, Division of Oral Biological Sciences, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan.
Akiko Mizokami *OBT Research Center, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan. akiko-k@dent.kyushu-u.ac.jp.
Sergio Romera-GinerComputational Biomedicine Laboratory, Prince Felipe Research Center (CIPF), 46012, Valencia, Spain.
Jaime Llera-OyolaComputational Biomedicine Laboratory, Prince Felipe Research Center (CIPF), 46012, Valencia, Spain.
Yosuke YamawakiDepartment of Advanced Pharmacology, Daiichi University of Pharmacy, 22-1 Tamagawa-Cho, Minami-Ku, Fukuoka, 815-8511, Japan.
Tomomi SanoDepartment of Cell Biology, Aging Science, and Pharmacology, Division of Oral Biological Sciences, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan.
Eijiro JimiOBT Research Center, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan.
Francisco García-GarcíaComputational Biomedicine Laboratory, Prince Felipe Research Center (CIPF), 46012, Valencia, Spain.
Takashi KanematsuDepartment of Cell Biology, Aging Science, and Pharmacology, Division of Oral Biological Sciences, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan.

Funding

Japan Science and Technology Agency SPRING JPMJSP2136Japan Society for the Promotion of Science 22K09904Ministerio de Ciencia e Innovación PID2021-124430OA-I00
6 · The paper itself

Abstract

backgroundSignificant sex differences exist in the prevalence and incidence of Alzheimer's disease (AD). Notably, testosterone has been reported to regulate cognitive functions in the brain, with low serum testosterone levels correlating with increased AD risk. However, the specific mechanisms underlying this relationship remain unclear. Recent studies have demonstrated that microglia, the primary innate immune cells in the brain, play a crucial role in AD development. Therefore, this study aimed to explore sex differences in microglial function, specifically focusing on the role of testosterone in miRNA-mediated regulation of microglial gene expression.

methodsMicroglia were isolated from pooled hippocampal tissue of five 8-month-old male and female mice. Total RNA was extracted and subjected to miRNA microarray analysis. The mouse microglial cell line MG6 was used for in vitro experiments. Following testosterone treatment, miRNA, gene, and protein expression levels were investigated. An inflammatory response was induced using lipopolysaccharide (LPS) stimulation, and subsequent p65 phosphorylation was assessed.

resultsSex-dependent differences were observed in miRNA-mediated biological processes, with males exhibiting greater changes. Male-enriched miRNAs were associated with fatty acid synthesis and metabolism pathways. In MG6 cells, testosterone treatment upregulated the expression of several miRNAs enriched in male microglia, particularly those targeting genes related to fatty acid synthesis. Additionally, testosterone significantly reduced the gene expression of fatty acid synthase (FASN). This testosterone-induced inhibition of FASN expression attenuated NF-κB/p65 phosphorylation. Consequently, the suppression of FASN expression led to reduced expression and secretion of tumor necrosis factor-alpha following LPS stimulation in MG6 cells.

conclusionsThese findings suggest that testosterone modulates inflammation in male microglia by regulating fatty acid synthesis, potentially contributing to the observed sex differences in AD pathogenesis.

Indexed as

Fatty AcidsMicrogliaMicroRNAsNeuroinflammatory DiseasesSex CharacteristicsSignal TransductionAnimalsCell LineFemaleLipopolysaccharidesMaleMiceMice, Inbred C57BLTestosteroneFatty AcidsLipopolysaccharidesMicroRNAsTestosteroneFatty acid synthesisInflammationMicrogliamiRNASex differencesTestosterone

Identifiers

PMID39905477
PMCPMC11792555

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.