Sleep and Wake Affect Glycogen Content and Turnover at Perisynaptic Astrocytic Processes

Area of Science:

• Neuroscience
• Cellular Biology
• Metabolism

Background:

• Astrocytic glycogen is the brain's sole glucose reserve, producing lactate for neuronal energy.
• Brain metabolism is higher during wakefulness than sleep, suggesting a dynamic regulation of glycogen.
• Previous studies on brain glycogen dynamics during sleep/wake cycles yielded inconsistent results due to whole-tissue measurements.

Purpose of the Study:

• To investigate the dynamics of astrocytic glycogen specifically in the perisynaptic space across different sleep-wake states.
• To test the hypothesis that wakefulness depletes glycogen and sleep replenishes it at the synaptic level.
• To explore the impact of sleep restriction on glycogen localization and content.

Main Methods:

• Utilized tridimensional electron microscopy to quantify glycogen granules in astrocytic processes surrounding axon-spine synapses in the mouse frontal cortex.
• Compared glycogen content after periods of sleep, spontaneous wake, forced wake, and chronic sleep restriction.
• Analyzed the number, size, and estimated glucose content of glycogen granules.

Main Results:

• Wakefulness, regardless of duration or type (spontaneous/forced), increased the number of perisynaptic glycogen granules compared to sleep.
• Longer wake periods correlated with smaller glycogen granules, indicating increased turnover.
• Despite increased granule numbers during wake, the total estimated glucose content was lower than during sleep, suggesting sleep favors glucose storage.
• Chronic sleep restriction led to glycogen granules moving closer to the synaptic cleft.

Conclusions:

• Both short and prolonged wakefulness increase glycogen turnover in astrocytic processes surrounding synapses.
• Sleep appears to promote glycogen accumulation and storage in these perisynaptic regions.
• These findings highlight the critical role of astrocytes and their glycogen stores in regulating brain energy homeostasis across the sleep-wake cycle.