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

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.