Why target brain adenosine receptors? A historical perspective.

The quest for a non-dopaminergic approach to treating Parkinson's disease (PD) has been quietly progressing over the past several decades, and is now finding its momentum. Here, in what is more a memoir than a comprehensive review, we discuss work carried out over the past 50 years to show that adenosine acts as a critical signaling molecule via actions against a specific family of receptors. Importantly for PD, adenosine A receptors have a selective localization to the basal ganglia and specifically to the indirect output pathway, offering a targeted, non-dopaminergic opportunity to modulate basal ganglia output.

Acute doses of caffeine shift nervous system cell expression profiles toward promotion of neuronal projection growth.

Caffeine is a widely consumed psychoactive substance, but little is known about the effects of caffeine stimulation on global gene expression changes in neurons. Here, we conducted gene expression profiling of human neuroepithelial stem cell-derived neurons, stimulated with normal consumption levels of caffeine (3 μM and 10 μM), over a period of 9 h. We found dosage-dependent activation of immediate early genes after 1 h.

Adenosine and Sleep.

The classic endogenous somnogen adenosine promotes sleep via A and A receptors. In this chapter, we present an overview of the current knowledge regarding the regulation of adenosine levels, adenosine receptors, and available pharmacologic and genetic tools to manipulate the adenosine system. This is followed by a summary of current knowledge of the role of adenosine and its receptors in the regulation of sleep and wakefulness.