Cordycepin Increases Nonrapid Eye Movement Sleep via Adenosine Receptors in Rats

Zhenzhen Hu,Ki-Wan Oh,Chung-Il Lee,Eun-Hye Oh,Kinam Lee,Jin Tae Hong,Jae-Ryong Bae,Jin-Yi Han,Myong-Soo Chong,Vikash Kumar Shah

doi:10.1155/2013/840134

Abstract

Cordycepin (3′-deoxyadenosine) is a naturally occurring adenosine analogue and one of the bioactive constituents isolated from Cordyceps militaris/Cordyceps sinensis, species of the fungal genus Cordyceps. It has traditionally been a prized Chinese folk medicine for the human well-being. Because of similarity of chemical structure of adenosine, cordycepin has been focused on the diverse effects of the central nervous systems (CNSs), like sleep regulation. Therefore, this study was undertaken to know whether cordycepin increases the natural sleep in rats, and its effect is mediated by adenosine receptors (ARs). Sleep was recorded using electroencephalogram (EEG) for 4 hours after oral administration of cordycepin in rats. Sleep architecture and EEG power spectra were analyzed. Cordycepin reduced sleep-wake cycles and increased nonrapid eye movement (NREM) sleep. Interestingly, cordycepin increased θ (theta) waves power density during NREM sleep. In addition, the protein levels of AR subtypes (A1, A2A, and A2B) were increased after the administration of cordycepin, especially in the rat hypothalamus which plays an important role in sleep regulation. Therefore, we suggest that cordycepin increases theta waves power density during NREM sleep via nonspecific AR in rats. In addition, this experiment can provide basic evidence that cordycepin may be helpful for sleep-disturbed subjects.

Highlights

Purines are ubiquitous molecules with important roles in the regulation of metabolic networks and signal transduction events
Further research showed that systemic administration of adenosine, its analogs, or inhibitors of its metabolism increase nonrapid eye movement (NREM) sleep in rodents, especially [3]
It will be suggested that cordycepin, an adenosine analogue, plays a role in the modulation of theta oscillations in NREM sleep

Summary

Introduction

Purines are ubiquitous molecules with important roles in the regulation of metabolic networks and signal transduction events. In the central nervous systems (CNSs), adenosine and ATP modulate the sleep-wake cycles, acting as ligands of specific transmembrane receptors and as allosteric effectors of key intracellular enzymes for brain energy expenditure [1]. Adenosine levels are influenced by neuronal activity. ATP release from astrocytes contributes to extracellular levels of adenosine that have a powerful modulatory effect on synaptic transmission [2]. The role of this astrocyte-derived adenosine in sleep-waking homeostasis was recently investigated. Further research showed that systemic administration of adenosine, its analogs, or inhibitors of its metabolism increase nonrapid eye movement (NREM) sleep in rodents, especially [3]

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