Low-dose diazepam improves cognitive function in APP/PS1 mouse models: Involvement of AMPA receptors.

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  • Additional Information
    • Source:
      Publisher: Elsevier/North-Holland Biomedical Press Country of Publication: Netherlands NLM ID: 0045503 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-6240 (Electronic) Linking ISSN: 00068993 NLM ISO Abbreviation: Brain Res Subsets: MEDLINE
    • Publication Information:
      Original Publication: Amsterdam Elsevier/North-Holland Biomedical Press.
    • Subject Terms:
      Receptors, AMPA*/metabolism ; Alzheimer Disease*/drug therapy ; Alzheimer Disease*/metabolism ; Diazepam*/pharmacology ; Disease Models, Animal* ; Cognition*/drug effects ; Mice, Transgenic* ; Amyloid beta-Protein Precursor*/genetics ; Amyloid beta-Protein Precursor*/metabolism ; Neuroprotective Agents*/pharmacology; Animals ; Mice ; Male ; Amyloid beta-Peptides/metabolism ; Neurons/drug effects ; Neurons/metabolism ; Cognitive Dysfunction/drug therapy ; Cognitive Dysfunction/metabolism ; Presenilin-1/genetics ; Mice, Inbred C57BL
    • Abstract:
      Previous studies have indicated a close association between cognitive impairment in patients with neurodegenerative diseases, such as Alzheimer's disease (AD), and synaptic damage. Diazepam (DZP), a benzodiazepine class drug, is used to control symptoms such as seizures, anxiety, and sleep disorders. These symptoms can potentially manifest throughout the entire course of AD. Therefore, DZP may be utilized in the treatment of AD to manage these symptoms. However, the specific role and mechanisms of DZP in AD remain unclear. In this study, we discovered that long-term administration of a low dose of DZP (0.5  mg/kg) improved cognitive function and protected neurons from damage in APP/PS1 mice. Mechanistic investigations revealed that DZP exerted its neuroprotective effects and reduced Aβ deposition by modulating GluA1 (glutamate AMPA receptor subunit) to influence synaptic function. In conclusion, these findings highlight the potential benefits of DZP as a novel therapeutic approach, suggesting that long-term use of low-dose DZP in early-stage AD patients may be advantageous in slowing disease progression.
      Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
      (Copyright © 2024 Elsevier B.V. All rights reserved.)
    • Contributed Indexing:
      Keywords: AMPA receptor; Alzheimer’s disease; Cognitive impairment; Diazepam; GluA1; Neuroprotective effects; Synapse
    • Accession Number:
      0 (Receptors, AMPA)
      Q3JTX2Q7TU (Diazepam)
      0 (Amyloid beta-Protein Precursor)
      0 (Neuroprotective Agents)
      0 (Amyloid beta-Peptides)
      0 (Presenilin-1)
    • Publication Date:
      Date Created: 20240830 Date Completed: 20241116 Latest Revision: 20241116
    • Publication Date:
      20241118
    • Accession Number:
      10.1016/j.brainres.2024.149207
    • Accession Number:
      39214326