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@ARTICLE{Ruoff:282576,
      author       = {Ruoff, Lisa Katharina and Bänfer, Irina Wanda Helene and
                      Liedtke, Djavid Elias and China, Sofie Elena and Wiltfang,
                      Jens and Bayer, Thomas A and Bock, Sören Frederik and
                      Spandau, Friederike and Bouter, Caroline and Beindorff,
                      Nicola and Bouter, Yvonne},
      title        = {{L}ong-term thiethylperazine treatment in the {T}g4-42
                      mouse model of {A}lzheimer's disease mouse: {T}herapeutic
                      potential vs. adverse effects.},
      journal      = {Pharmacology, biochemistry and behavior},
      volume       = {258},
      issn         = {0091-3057},
      address      = {Amsterdam [u.a.]},
      publisher    = {Elsevier Science},
      reportid     = {DZNE-2025-01336},
      pages        = {174127},
      year         = {2025},
      abstract     = {Alzheimer's disease (AD) is a neurodegenerative disorder
                      characterized by progressive cognitive decline and
                      behavioral impairments. Thiethylperazine, a dopamine
                      receptor antagonist with antiemetic and antidopaminergic
                      properties, has been proposed as a potential therapeutic
                      agent for AD. However, its impact on cognitive function in
                      AD remains unclear.This study investigated the long-term
                      effects of thiethylperazine on memory, anxiety-like
                      behavior, motor function, and AD pathology in Tg4-42 mice, a
                      model characterized by Aβ4-42 overexpression and
                      progressive neurodegeneration. Additionally, the impact of
                      prolonged thiethylperazine treatment on behavioral outcomes
                      and cerebral glucose metabolism in healthy adult C57BL/6J
                      wild-type (WT) mice were examined.Tg4-42 and WT mice were
                      treated daily with 10 mg/kg thiethylperazine for 6 months,
                      starting at 10 weeks of age. Memory, anxiety-related, and
                      motor tests were performed at 7.5 months.
                      Immunohistochemical analyses were conducted to quantify
                      effects on Aβ pathology, neurogenesis, neuron number, and
                      neuroinflammation. Additionally, 18F-FDG-PET imaging was
                      used to evaluate metabolic activity in WT mice following
                      treatment.Thiethylperazine improved recognition memory in
                      Tg4-42 mice in the Novel Object Recognition test and
                      exhibited anxiolytic properties. However, it impaired
                      spatial learning in the Morris Water Maze (MWM), reduced
                      locomotion, and failed to mitigate motor impairments. No
                      effects on neuron loss or neuroinflammation were observed.
                      In WT mice, thiethylperazine altered learning processes in
                      the MWM, as indicated by shifts in search strategies,
                      induced hypometabolism and increased neurogenesis.Although
                      thiethylperazine offers mild cognitive benefits in Tg4-42,
                      its adverse effects on learning strategies and locomotion
                      raise questions about its potential as a therapeutic option
                      for AD.},
      keywords     = {(18)F-FDG PET (Other) / (Up to seven): Tg4-42 mouse model
                      (Other) / Dopamine receptor antagonist (Other) / Morris
                      water maze (Other) / Neurogenesis (Other) / Novel object
                      recognition (Other)},
      cin          = {AG Wiltfang},
      ddc          = {540},
      cid          = {I:(DE-2719)1410006},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41218709},
      doi          = {10.1016/j.pbb.2025.174127},
      url          = {https://pub.dzne.de/record/282576},
}