Imagine you’re lost in a maze, feeling anxious and unsure of which way to turn. Now imagine finding a secret door that leads to a peaceful garden, instantly calming your nerves. In a similar way, scientists have discovered that activating VTAVgat neurons in the brains of APP/PS1 mice can alleviate anxiety caused by acute social defeat stress (SDS). Just like finding that serene garden, these neurons act as a key to unlock relief from anxiety. The researchers conducted tests using the open field and elevated plus-arm tests to measure anxiety-related behaviors in the mice. They found that when VTAVgat neurons were activated, sleep duration increased due to decreased sleep latency and increased non-rapid eye movement (NREM) sleep. However, the quality of sleep was poor. To address this, the scientists chemogenetically activated VTAVgat neurons using deschloroclozapine, which improved sleep quality and relieved SDS-induced anxiety. These findings suggest that poor sleep quality may worsen anxiety in Alzheimer’s disease (AD) and highlight the potential of targeting VTAVgat neurons as a therapeutic approach. To learn more about this fascinating research, explore the link below!

IntroductionAlzheimer’s disease (AD) is a progressive neurodegenerative disease that results in cognitive impairment and is often accompanied by anxiety. In this study, we investigated whether the activation of VTAVgat neurons could reduce anxiety in APP/PS1 mice. We hypothesized that acute social defeat stress (SDS) would lead to anxiety in APP/PS1 mice, and that the activation of VTAVgat neurons would alleviate this anxiety.MethodsWe exposed APP/PS1 mice to acute SDS and assessed anxiety using the open field test and elevated plus-arm test. Activated VTAVgat neurons was tested by cfos staining. Sleep quality was detected using electroencephalogram after SDS or non-SDS procedure. Sleep duration, sleep latency, and non-rapid eye movement (NREM) percentage were analyzed. VTAVgat neurons were chemogenetically activated by deschloroclozapine.ResultsOur results showed that acute SDS led to anxiety in APP/PS1 mice, as evidenced by increased anxiety-related behaviors in the open field and elevated plus-arm tests. Activation of VTAVgat neurons by SDS led to an increase in sleep duration, primarily due to a decrease in sleep latency and an increase in NREMs. However, the quality of sleep was poor. Chemogenetical activation of VTAVgat neurons improved sleep quality and relieved SDS-induced anxiety. Furthermore, the anxiety state correlated negatively with sleep duration and NREM percentage and correlated positively with theta power density in APP/PS1 mice.DiscussionOur study provides evidence that the activation of VTAVgat neurons alleviates SDS-induced anxiety in APP/PS1 mice, suggesting that poor sleep quality may exacerbate anxiety in AD. These findings may have important implications for the treatment of anxiety in AD, as targeting VTAVgat neurons could be a potential therapeutic approach.

Read Full Article (External Site)