Chronic Sleep Disruption Activates the Transcriptional Unfolded Protein Response and Induces Compartment-Specific Proteomic Changes in Mice

Chronic sleep disruption in mice triggers a modest global transcriptional stress response but produces stronger, compartment-specific proteomic changes, including synaptic alterations linked to synaptic vesicle endocytosis and spine morphogenesis.

• Why it matters: The mechanisms connecting chronic sleep disruption to adverse brain health and higher dementia risk, including Alzheimer’s disease, are not well defined, especially at vulnerable synapses over time.
• What they did: Mice were exposed to chronic sleep disruption, then researchers profiled brain transcriptomic signatures and subcellular compartment-specific proteomes, comparing synaptosomal (P2) fractions with whole-brain proteomes.
• The result: Chronic sleep disruption caused unique synaptic proteomic shifts distinct from whole-brain immune/glial and neuronal changes, alongside subtle CA1 ultrastructural effects—reduced pre-synapse size and decreased synaptic vesicle density—suggesting altered synaptic transmission and plasticity.

AI summary of the abstract · may contain errors · not medical advice · read the paper.