Description
Naked mole rats (NMRs) exhibit unique physiological adaptations including extraordinary resistance to hypoxia and anoxia. NMR exhibit a wide range of metabolic adaptations likely evolved to survive within their harsh environment. Amongst these, is significantly elevated brain glycogen levels compared to other species like mice, providing NMRs with energetic substrate during periods of hypoxia/anoxia. During anoxia, NMRs significantly reduce physiological and brain activities, employing survival strategies for oxygen-limited environments.
Astrocytes, the primary site of glycogen storage in the adult brain, are essential for maintaining neuronal function by metabolizing glycogen and providing lactate during metabolic stress. This process is regulated by cyclic adenosine monophosphate (cAMP), which plays a central role in glycogen breakdown and lactate production. Soluble adenylyl cyclase (sAC), a bicarbonate-sensitive enzyme, drives cAMP production in astrocytes, linking their metabolic activity to neuronal demands under varying oxygen conditions.
In addition to cAMP, our findings reveal that cyclic cytidine monophosphate (cCMP), a structurally similar yet less-studied nucleotide, is significantly elevated in NMR brain tissue during anoxia. While cCMP's precise role is still being elucidated, its increase alongside cAMP suggests a potential cooperative function in astrocyte-neuron metabolic communication during oxygen deprivation.
This study aims to understand if cCMP contributes to regulating glycogen metabolism and lactate production in astrocytes, enhancing NMRs' extraordinary tolerance to anoxic conditions. By exploring this novel signaling pathway, we aim to uncover key metabolic strategies that support neuroprotection in low-oxygen environments.