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@ARTICLE{Rajput:276092,
      author       = {Rajput, Mansi and Malik, Ihtzaz Ahmed and Methi, Aditi and
                      Cortes-Silva, Jonathan-Alexis and Fey, Dorothea and Wirths,
                      Oliver and Fischer, André and Wilting, Jörg and von Arnim,
                      Christine A F},
      title        = {{C}ognitive decline and neuroinflammation in a mouse model
                      of obesity: {A}n accelerating role of ageing.},
      journal      = {Brain, behavior and immunity},
      volume       = {125},
      issn         = {0889-1591},
      address      = {Orlando, Fla. [u.a.]},
      publisher    = {Elsevier},
      reportid     = {DZNE-2025-00173},
      pages        = {226 - 239},
      year         = {2025},
      abstract     = {Obesity, a pandemic, worldwide afflicts almost one billion
                      people. Obesity and ageing share several pathological
                      pathways leading to neurological disorders. However, due to
                      a lack of suitable animal models, the long-term effects of
                      obesity on age-related disorders- cognitive impairment and
                      dementia have not yet been thoroughly investigated.
                      Therefore, the current investigation focuses on developing a
                      suitable model to explore the effects of obese-ageing. It
                      also aims to determine whether obesity affects cognitive
                      abilities in an age-dependent manner, and to identify a
                      potential biomarker(s) for cognitive decline. Cognitive
                      tests were carried out on 6-months and 1-year-old
                      melanocortin-4 receptor (Mc4r)-deficient-obese and lean
                      (wildtype) mice. Additionally, brains and sera were
                      harvested for molecular, histological and serological
                      analyses from 6, 12, and 24-months-old mice. Finally, RT-PCR
                      was carried out after hippocampal mRNA sequencing. The
                      cognitive tests revealed that 1-year-old obese mice have
                      cognitive impairment along with underlying neurodegenerative
                      changes, such as enlarged lateral ventricles. Serum
                      neurofilament light chain (sNfL) levels were also elevated.
                      Lipid accumulation and neuroinflammation were apparent
                      besides, a compromised blood-brain barrier (BBB) indicated
                      by altered junction protein gene expression.
                      Differentially-expressed genes associated with cognitive
                      decline were identified by mRNA sequencing of hippocampi.
                      One such gene, Secreted Phosphoprotein 1 (Spp1) had markedly
                      increased expression in cognitively-impaired obese mice. Our
                      findings present an obese-aged mouse model of cognitive
                      decline with neuroinflammation, reduced BBB-integrity and
                      predisposing neurodegenerative changes. Obese-ageing
                      accelerates the progression of cognitive impairment.
                      Furthermore, Spp1 appears to be a potential biomarker for
                      early diagnosis of neuropathological disorders.},
      keywords     = {Ageing (Other) / Cognitive decline (Other) /
                      Neuroinflammation (Other) / Obesity (Other)},
      cin          = {AG Fischer},
      ddc          = {150},
      cid          = {I:(DE-2719)1410002},
      pnm          = {352 - Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:39730092},
      doi          = {10.1016/j.bbi.2024.12.154},
      url          = {https://pub.dzne.de/record/276092},
}