The Bioenergetic Network of Adenosine in Hibernation, Sleep, and Thermoregulation

Neural Signaling Metabolites May Modulate Energy Use in Hibernation

“…Adenosine is a likely candidate as an endogenous A 1 AR agonist that is capable of driving the onset of torpor based on the purine’s role in sleep 45 , thermoregulation 39, 53 and energy homeostasis 59 . Adenosine is a neuroprotective neuromodulator and by-product of cellular metabolism that is positioned within neurons, astrocytes and peripheral tissues to modulate brain and systemic energy homeostasis through integrated biochemical and receptor mediated processes.…”

Adenosine and P1 receptors: Key targets in the regulation of sleep, torpor, and hibernation

“…Sleep, torpor, and hibernation are integral to energy balance. At the same time, adenosine which is a homeostatic bioenergetic network regulator appears to accumulate before entry into the three states, suggesting that adenosine and P1 receptors, may mediate sleep, torpor and hibernation (Drew and Jinka, 2013;Silvani et al, 2018). Much evidence suggests that activation or inhibition of the central nervous system (CNS) adenosine receptors by genetic or pharmacological means can alter the states of sleep, torpor, and hibernation.…”

“…Adenosine is a purine nucleoside involved in many signaling pathways of energy homeostasis. One of the functions of sleep is to restore brain energy homeostasis, while the primary function of hibernation and torpor is to restore or protect body energy homeostasis (Drew and Jinka, 2013). According to many previous studies, adenosine A 1 receptors and A 2A receptors (A 1 Rs and A 2A Rs) play an essential role in inducing NREM, the activation of A 1 R and A 3 receptors (A 3 Rs) may induce torpor (Silvani et al, 2018), and the onset of hibernation may be due to the activation of A 1 Rs (Jinka et al, 2011;Frare and Drew, 2021).…”