{
  "abstract": "Introduction: A Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by both motor and non-motor symptoms, including depression, which markedly impairs patients’ quality of life. Although sex differences have been described in PD progression, the mechanisms underlying gender-specific susceptibility to depressive symptoms remain poorly understood.\n\nMethods: This study investigated sex-dependent differences in depressive-like behaviors and their underlying molecular mechanisms in an in vivo model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic degeneration, using adult male and female CD1 mice.\n\nResults: Our results demonstrated that MPTP administration induced nigrostriatal degeneration and α-synuclein accumulation in both sexes, with more pronounced alterations in males. Male mice also exhibited greater depressive- and anxiety-like behaviors, accompanied by a marked reduction in 5-HT2C receptor expression, increased hippocampal acetylcholine levels, impaired expression of the synaptic markers PSD-95 and synaptophysin, and a stronger downregulation of the BDNF/PI3K/AKT pathway compared with females.\n\nDiscussion: These findings demonstrate that sex significantly influences vulnerability to PD-associated depressive symptoms, with males showing greater behavioral and molecular impairment. Overall, our results highlight the importance of considering sex as a biological variable in PD research and support the development of personalized therapeutic strategies targeting non-motor symptoms.",
  "abstract_shown": true,
  "affiliations": [
    "Research Operative Unit of Neuropharmacology and Translational Neurosciences, Oasi Research Institute",
    "Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Mannino Deborah"
    },
    {
      "affs": [
        1
      ],
      "name": "Cucinotta Laura"
    },
    {
      "affs": [
        1
      ],
      "name": "Basilotta Rossella"
    },
    {
      "affs": [
        1
      ],
      "name": "Labellarte Davide"
    },
    {
      "affs": [
        1
      ],
      "name": "Esposito Emanuela"
    },
    {
      "affs": [
        1
      ],
      "name": "Campolo Michela"
    },
    {
      "affs": [
        1
      ],
      "name": "Paterniti Irene"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/50ptmjspd1afg.bib",
  "cited_by": 0,
  "doi": "10.3389/fphar.2026.1961464",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13732771/",
  "id": "50ptmjspd1afg",
  "issns": [
    "1663-9812"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1961464/full",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Research"
    ],
    [
      "openalex",
      "2728|Parkinson's Disease Mechanisms and Treatments"
    ]
  ],
  "openalex": "W7223092493",
  "pdf_url": "https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2026.1961464/pdf",
  "pmcid": "PMC13732771",
  "pmid": "42985056",
  "published": "2026-10-21",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/50ptmjspd1afg.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:06Z",
      "native_id": "10.3389/fphar.2026.1961464",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fphar.2026.1961464/full"
    },
    {
      "first_seen": "2026-11-08T12:22:41Z",
      "native_id": "PMC13732771",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fphar.2026.1961464"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2728|Parkinson's Disease Mechanisms and Treatments",
      "subfield": "neurology"
    }
  ],
  "title": "Gender differences in depressive-like behavior in Parkinson’s disease",
  "title_text": "Gender differences in depressive-like behavior in Parkinson’s disease",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T12:22:41Z",
  "url": "https://research.draconitic.com/paper/50ptmjspd1afg",
  "venue": "Frontiers in Pharmacology",
  "versions": []
}