{
  "abstract": "c-Jun N-terminal kinase (JNK) regulates stress responses and affective behaviour, but the neural populations mediating these effects remain unclear. Here, we delivered a nucleus-targeted JNK inhibitor to the mouse brain using blood-brain barrier-crossing adeno-associated virus vectors with distinct cellular tropisms. JNK inhibition produced strikingly different behavioural outcomes depending on the neuronal populations targeted. Only AAV-PHP.eB-hSyn1-mediated delivery reproduced the previously reported anxiolytic phenotype, whereas AAV.CAP-B10-hSyn1 increased locomotor activity and depressive-like behaviour and AAV.CAP-B10-mDlx reduced locomotion while enhancing object recognition memory. The anxiolytic response was accompanied by reduced hilar mossy cell abundance and an approximately two-fold increase in doublecortin-positive newborn granule neurons in the dentate gyrus. Notably, this phenotype mirrors our previous findings following selective JNK inhibition in adult hippocampal progenitor cells, implicating the neurogenic niche as a convergent substrate for anxiolytic responses to JNK inhibition. Proteomic analysis of plasma extracellular vesicles revealed widespread alterations in metabolic and inflammatory proteins upon JNK inhibition, despite neuron-restricted transgene expression. Together, these findings demonstrate that the behavioural and systemic consequences of JNK inhibition depend critically on the neural populations targeted and identify hippocampal neurogenesis-associated circuits involving mossy cells as candidate mediators of JNK-dependent anxiety regulation.",
  "abstract_shown": true,
  "affiliations": [
    "Turku Bioscience Centre, University of Turku and Abo Akademi University"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "name": "A. Jokela"
    },
    {
      "name": "N. Tiwari"
    },
    {
      "name": "D. Flinkman"
    },
    {
      "name": "S. Abyari"
    },
    {
      "name": "P. Deshpande"
    },
    {
      "name": "J. M. John"
    },
    {
      "affs": [
        0
      ],
      "name": "E. Coffey"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/aq9re9j5mc4gx.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.30.763057",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.30.763057v1.full",
  "id": "aq9re9j5mc4gx",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.30.763057v1",
  "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": null,
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.30.763057v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-30",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/aq9re9j5mc4gx.ris",
  "sources": [
    {
      "first_seen": "2026-11-10T00:27:11Z",
      "native_id": "10.64898/2026.10.30.763057",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.30.763057v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:neuroscience",
      "subfield": "neuroscience"
    }
  ],
  "title": "Targeting distinct neuronal populations with AAV vectors reveals neurogenesis-associated anxiolytic effects of JNK inhibition",
  "title_text": "Targeting distinct neuronal populations with AAV vectors reveals neurogenesis-associated anxiolytic effects of JNK inhibition",
  "type": "preprint",
  "updated_at": "2026-11-10T00:27:11Z",
  "url": "https://research.draconitic.com/paper/aq9re9j5mc4gx",
  "venue": "bioRxiv",
  "versions": []
}