Astrocyte glycogen metabolism is required for neural activity during aglycemia or intense stimulation in mouse white...

Area of Science:

• Neuroscience
• Cellular Physiology
• Biochemistry

Background:

• Neural function relies on energy supply, with glycogen serving as a crucial energy reserve in the central nervous system.
• Understanding glycogen's role in maintaining axon function during metabolic stress is vital for neurological health.

Purpose of the Study:

• To investigate if inhibiting glycogen degradation accelerates compound action potential (CAP) failure in the mouse optic nerve (MON) during aglycemia or high-intensity stimulation.
• To elucidate the physiological role of glycogen metabolism in sustaining neural activity.

Main Methods:

• Assessed axon function via evoked CAP and measured biochemical glycogen content in mouse optic nerves.
• Utilized isofagomine, a novel inhibitor of CNS glycogen phosphorylase, to modulate glycogen metabolism.
• Exposed MONs to glucose-free artificial cerebrospinal fluid (aCSF) and high-frequency stimulation under varying glucose concentrations.

Main Results:

• Isofagomine significantly increased glycogen content under normoglycemic conditions.
• Inhibition of glycogenolysis accelerated CAP failure during aglycemia and high-frequency stimulation.
• Despite increased glycogen stores, CAP failure was not delayed when glycogen metabolism was inhibited, indicating its necessity for energy supply.

Conclusions:

• Glycogen metabolism plays a critical role in sustaining neural function during periods of aglycemia and high-intensity neural activity.
• Inhibiting glycogen breakdown impairs the optic nerve's ability to maintain function under metabolic stress.
• These findings highlight the importance of glycogen as an energy substrate for axonal function.