{
  "id": 6283179,
  "title": "Sex-divergent responses to microglial depletion suggest distinct regulatory dependencies in the aged brain",
  "url": "https://urgent.news/2026/09/08/sex-divergent-responses-to-microglial-depletion-suggest-distinct",
  "topic": "science",
  "section": "Science",
  "published": "2026-09-08T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.09.03.745468v1?rss=1"
  },
  "original_language": "en",
  "account": "Microglia play a crucial role in maintaining brain homeostasis, but their functions in elderly mice are not well understood. To investigate, researchers analyzed microRNA (miRNA) profiles, cellular-resolution spatial transcriptomics, and bulk proteomics in 21-month-old mice. They specifically examined the effects of microglial depletion via CSF1R inhibition (PLX5622 treatment). Across various brain regions, microglia-enriched miRNAs, particularly miR-146a-5p and miR-223-3p, were found to be downregulated in both male and female mice.\n\nThe researchers then observed sex-dimorphic transcriptional responses. In females, the changes were predominantly cell-type specific, while in males, they were bidirectional. This included upregulation of genes such as Lzts3, Shank3, and Fgfbp1, alongside downregulation of Ang. On the proteomic level, changes were significantly larger and independent of mRNA alterations: males showed 295 differentially expressed proteins (DEPs), while females had 34 (an 8.7-fold difference). Among the male DEPs, there were opposing directional shifts: upregulation of synaptic vesicle proteins and downregulation of proteins involved in mitochondrial ATP synthesis. These findings reveal sex-dimorphic molecular consequences of microglial loss in the aged brain and highlight potential post-transcriptional mechanisms that require further exploration.",
  "summary": "Microglia are essential for brain homeostasis, yet their roles in the aged brain remain poorly defined. Using microRNA (miRNA) profiling, cellular-resolution spatial transcriptomics, and bulk proteomics in 21-month-old mice, we characterize sex-dimorphic responses to microglial depletion via CSF1R inhibition (PLX5622 treatment). Microglia-enriched miRNAs, notably miR-146a-5p and miR-223-3p, were…",
  "key_points": [],
  "editors_take": null,
  "illustration": null,
  "coverage": {
    "outlets": 1,
    "also_reported_by": []
  },
  "ai_generated": true,
  "disclaimer": "Summaries, key points and the editor’s take are written by software from other outlets’ reporting and may contain errors — always check the linked original."
}