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Glymphatic clearance controls state-dependent changes in brain lactate concentration.

Iben Lundgaard¹, Minh Lon Lu^1,2, Ezra Yang¹

¹1 Center for Translational Neuromedicine, Department of Neurosurgery, University of Rochester, Rochester, NY, USA.

Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism

|August 3, 2016

Summary

The glymphatic system regulates brain lactate levels, decreasing them during sleep. Impaired glymphatic function prevents this lactate decline, highlighting its role in brain energy metabolism and the sleep-wake cycle.

Keywords:

Metabolism astrocytes cerebrospinal fluid glymphatic system lactate stroke

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Simultaneous Electroencephalography, Real-time Measurement of Lactate Concentration and Optogenetic Manipulation of Neuronal Activity in the Rodent Cerebral Cortex

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Published on: December 19, 2012

Area of Science:

Neuroscience
Sleep Science
Brain Metabolism

Background:

Brain lactate concentration exhibits state-dependent variations, being higher during wakefulness than sleep.
The underlying mechanisms for arousal-linked increases and sleep-associated declines in brain lactate remain unclear.

Purpose of the Study:

To investigate the role of the glymphatic system in regulating brain lactate concentration during changes in the sleep-wake cycle.
To elucidate the relationship between glymphatic function, brain lactate, and sleep-wake states.

Main Methods:

Mice were subjected to manipulations to suppress glymphatic function, including acetazolamide treatment, cisterna magna puncture, aquaporin 4 deletion, and altered body positioning.
Brain lactate levels were monitored during transitions between wakefulness, sleep, and anesthesia.
Lactate accumulation in cervical and inguinal lymph nodes was assessed in anesthetized mice.

Main Results:

Suppression of glymphatic function inhibited the normal decline in brain lactate observed upon transitioning to sleep or anesthesia.
Impaired glymphatic function led to reduced lactate accumulation in cervical lymph nodes.
Brain lactate concentration was found to be inversely correlated with glymphatic-lymphatic clearance.

Conclusions:

The glymphatic system is crucial for regulating state-dependent changes in brain lactate concentration.
Brain lactate serves as a biomarker for the sleep-wake cycle and may increase during sleep deprivation due to reduced glymphatic-lymphatic clearance.
This study reveals that the glymphatic-lymphatic system facilitates the export of incompletely oxidized glucose as lactate, offering new insights into brain energy metabolism.