{
  "abstract": "Background: Chronic D-galactose exposure produces selected behavioral and cellular changes associated with aging. We examined whether nicotine attenuates these changes and whether its effects differ between wild-type rats and α7 nicotinic acetylcholine receptor (α7-nAChR) knockout rats.\n\nMethods: Female and male rats received saline, D-galactose (180 mg/kg/day), or D-galactose plus nicotine (0.5 mg/kg/day) for 49 days. We assessed spatial behavior, hippocampal staining and gene expression, and peripheral biochemical measures. Nineteen animal endpoints were analyzed using sex × genotype × treatment models, with multiplicity-adjusted contrasts and unequal-variance sensitivity analyses. Exploratory hippocampal RNA sequencing included six wild-type rats per sex and treatment.\n\nResults: Compared with wild-type rats receiving D-galactose alone, nicotine-co-treated wild-type rats had shorter latency to first target entry, lower mean distance to the target, and more platform-site crossings in the water maze. They also had higher serum reduced glutathione (GSH) and lower hippocampal astrocytic and microglial immunoreactivity. The nicotine-associated increases in platform-site crossings and serum GSH, and the reduction in hippocampal ionized calcium-binding adapter molecule 1 (IBA1) immunoreactivity, were greater in wild-type than knockout rats. These differences were supported by both variance analyses. Nicotine co-treatment was also associated with reduced senescence-associated β-galactosidase staining and lower hippocampal App, Bace1, and Psen1 mRNA levels in wild-type rats. Serum amyloid-β1–42 did not change significantly. RNA sequencing identified treatment-associated expression patterns in wild-type hippocampi.\n\nConclusion: Nicotine attenuated selected D-galactose-associated behavioral and hippocampal alterations. The genotype comparisons support α7-nAChR-associated modulation of platform-site crossings, serum GSH, and hippocampal IBA1. They do not establish that changes in brain GSH or amyloid production mediate these effects, or that all nicotine responses share one receptor-dependent mechanism.",
  "abstract_shown": true,
  "affiliations": [
    "Beijing Life Science Academy , ,",
    "Key Laboratory of Tobacco Biological Effects , ,"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 12,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Xin Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Yue Li"
    },
    {
      "affs": [
        1
      ],
      "name": "Yingyan Li"
    },
    {
      "affs": [
        1
      ],
      "name": "Wenming Wang"
    },
    {
      "affs": [
        1
      ],
      "name": "Shuhao Ma"
    },
    {
      "affs": [
        1
      ],
      "name": "Jun Li"
    },
    {
      "affs": [
        0
      ],
      "name": "Xuan Cheng"
    },
    {
      "affs": [
        0
      ],
      "name": "Chunmei Guang"
    },
    {
      "affs": [
        0
      ],
      "name": "Enliang Hong"
    },
    {
      "affs": [
        0
      ],
      "name": "Huan Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "Hongwei Hou"
    },
    {
      "affs": [
        0
      ],
      "name": "Qingyuan Hu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/fxgcn453rdsee.bib",
  "cited_by": 0,
  "doi": "10.3389/fnagi.2026.1947643",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13724548/?tool=EBI",
  "id": "fxgcn453rdsee",
  "issns": [
    "1663-4365"
  ],
  "landing_url": "https://europepmc.org/article/PMC/PMC13724548",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Original Research"
    ],
    [
      "openalex",
      "2804|Antioxidants, Aging, Portulaca oleracea"
    ]
  ],
  "openalex": "W7222982088",
  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13724548/pdf/?tool=EBI",
  "pmcid": "PMC13724548",
  "pmid": "42973616",
  "published": "2026-10-19",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/fxgcn453rdsee.ris",
  "sources": [
    {
      "first_seen": "2026-11-03T15:20:50Z",
      "native_id": "PMC:PMC13724548",
      "source": "europepmc",
      "url": "https://europepmc.org/article/PMC/PMC13724548"
    },
    {
      "first_seen": "2026-11-04T12:23:06Z",
      "native_id": "PMC13724548",
      "source": "pmc",
      "url": "https://doi.org/10.3389/fnagi.2026.1947643"
    },
    {
      "first_seen": "2026-11-04T15:20:48Z",
      "native_id": "MED:42973616",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42973616"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2804|Antioxidants, Aging, Portulaca oleracea",
      "subfield": "neuroscience"
    }
  ],
  "title": "Nicotine attenuates D-galactose- induced hippocampal aging-like alterations with α7-nAChR- associated mechanisms",
  "title_text": "Nicotine attenuates D-galactose- induced hippocampal aging-like alterations with α7-nAChR- associated mechanisms",
  "type": "peer-reviewed",
  "updated_at": "2026-11-05T12:21:17Z",
  "url": "https://research.draconitic.com/paper/fxgcn453rdsee",
  "venue": "Frontiers in aging neuroscience",
  "versions": []
}