{
  "id": 17366070,
  "title": "Reduced cerebral blood flow and metabolic rate trigger an adaptive mitochondrial remodeling program in a Down syndrome mouse model",
  "url": "https://urgent.news/2026/10/31/reduced-cerebral-blood-flow-and-metabolic-rate-trigger-an-adaptive",
  "topic": "science",
  "section": "Science",
  "published": "2026-10-31T00:00:00.000Z",
  "source": {
    "name": "bioRxiv",
    "slug": "biorxiv",
    "url": "https://www.biorxiv.org/content/10.64898/2026.10.27.762261v1?rss=1"
  },
  "original_language": "en",
  "account": "Down syndrome (DS) is characterized by mitochondrial dysfunction, yet the extent of this impact on brain bioenergetics is not well understood. Utilizing a mouse model called Dp16(1)Yey/+ with ~115 extra copies of human chromosome 21 genes, researchers investigated brain-wide metabolic deficits in DS.\n\nThrough magnetic resonance imaging (MRI), the study found that Dp16 mice exhibit reduced cerebral blood flow and oxygen metabolic rate, with a more pronounced effect in males compared to females. Despite these metabolic reductions, mitochondrial respiratory capacity and ATP synthase activity remained largely intact across brain regions, although sex differences were observed.\n\nFurther analysis of gene expression revealed an upregulation of mitochondrial oxidative phosphorylation (OXPHOS) genes, indicating an adaptive response to meet bioenergetic demands. This mitochondrial remodeling program was most prominent in the male cortex and female cerebellum, suggesting a sex-specific response to metabolic stress.\n\nOverall, the findings demonstrate that the metabolic dysfunction in DS mice triggers an adaptive mitochondrial remodeling program throughout the brain. However, this compensatory mechanism does not fully normalize the metabolic deficits in Dp16 mice. Integrating functional assessments at the organismal and tissue levels with transcriptomic changes provides a comprehensive view of the physiological perturbations and adaptations in the DS brain, which may contribute to phenotypic outcomes associated with the condition.",
  "summary": "Mitochondrial dysfunction is a central feature of Down syndrome (DS), yet how trisomy 21 affects brain bioenergetics across scales--from gene transcription to cellular function to whole-brain metabolism--remains poorly understood. Here, we use the Dp16(1)Yey/+ (abbreviated Dp16) DS mouse model, which carries ~115 triplicated gene orthologs of human chromosome 21, to address this major knowledge…",
  "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."
}