{
  "abstract": "Low testosterone is linked to anxiety in men, but its causal role and underlying brain mechanisms remain unknown. Here, using outbred male rats stratified by natural variation in anxiety-like behaviour, we establish its causal endocrine contribution and uncover an astrocytic mitochondrial mechanism at the nucleus accumbens (NAc) blood-brain barrier (BBB). High-anxiety rats showed a NAc-selective increase in BBB permeability, alongside reduced astrocytic endfoot coverage, disrupted endfoot mitochondrial organisation and mitochondria-endoplasmic reticulum contacts, and lower mitofusin 2 (Mfn2). Testosterone suppression increased anxiety in low-anxiety rats, whereas physiological testosterone restoration reduced anxiety, reconfigured astrocytic mitochondrial and BBB-related transcriptional programmes, increased astrocytic endfoot coverage and Mfn2, recovering BBB permeability, with related effects in aged low-testosterone rats. NAc androgen receptor (AR) knockdown blunted behavioural and neurovascular responses, whereas NAc astrocyte-specific Mfn2 overexpression reduced anxiety. Thus, testosterone-AR signalling engages an astrocytic mitochondrial programme at the NAc neurovascular interface linking low testosterone to anxiety vulnerability.",
  "abstract_shown": true,
  "affiliations": [
    "Ecole Polytechnique Federale de Lausanne, Brain Mind Institute, Lausanne, Switzerland"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "name": "H. de Castro Abrantes"
    },
    {
      "name": "L. R. Depaauw-Holt"
    },
    {
      "name": "D. H. Ulgen"
    },
    {
      "name": "C. Di Giulio"
    },
    {
      "name": "M. Barbetti"
    },
    {
      "name": "E. Gebara"
    },
    {
      "name": "F. Hollis"
    },
    {
      "name": "J. L. Solano"
    },
    {
      "name": "L. Schlotterose"
    },
    {
      "name": "C. Menard"
    },
    {
      "name": "M. Salman"
    },
    {
      "name": "S. Astori"
    },
    {
      "affs": [
        0
      ],
      "name": "C. Sandi"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/d18874w6z73pv.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.03.749088",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.03.749088v1.full",
  "id": "d18874w6z73pv",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.03.749088v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "neuroscience"
    ],
    [
      "openalex",
      "2808|Barrier Structure and Function Studies"
    ]
  ],
  "openalex": "W7211938059",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.03.749088v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-03",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/d18874w6z73pv.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:15Z",
      "native_id": "10.64898/2026.09.03.749088",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.03.749088v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:neuroscience",
      "subfield": "neuroscience"
    }
  ],
  "title": "Low testosterone promotes anxiety through astrocytic mitochondrial remodelling at the nucleus accumbens blood-brain barrier",
  "title_text": "Low testosterone promotes anxiety through astrocytic mitochondrial remodelling at the nucleus accumbens blood-brain barrier",
  "type": "preprint",
  "updated_at": "2026-10-30T12:20:15Z",
  "url": "https://research.draconitic.com/paper/d18874w6z73pv",
  "venue": "bioRxiv",
  "versions": []
}