Extracellular ATP/adenosine dynamics in the brain and its role in health and disease

Abstract

Extracellular ATP and adenosine are neuromodulators that regulate numerous neuronal functions in the brain. Neuronal activity and brain insults such as ischemic and traumatic injury upregulate these neuromodulators, which exert their effects by activating purinergic receptors. In addition, extracellular ATP/adenosine signaling plays a pivotal role in the pathogenesis of neurological diseases. Virtually every cell type in the brain contributes to the elevation of ATP/adenosine, and various mechanisms underlying this increase have been proposed. Extracellular adenosine is thought to be mainly produced via the degradation of extracellular ATP. However, adenosine is also released from neurons and glia in the brain. Therefore, the regulation of extracellular ATP/adenosine in physiological and pathophysiological conditions is likely far more complex than previously thought. To elucidate the complex mechanisms that regulate extracellular ATP/adenosine levels, accurate methods of assessing their spatiotemporal dynamics are needed. Several novel techniques for acquiring spatiotemporal information on extracellular ATP/adenosine, including fluorescent sensors, have been developed and have started to reveal the mechanisms underlying the release, uptake and degradation of ATP/adenosine. Here, we review methods for analyzing extracellular ATP/adenosine dynamics as well as the current state of knowledge on the spatiotemporal dynamics of ATP/adenosine in the brain. We focus on the mechanisms used by neurons and glia to cooperatively produce the activity-dependent increase in ATP/adenosine and its physiological and pathophysiological significance in the brain.

Surface-Enhanced Raman Scattering Nanosensing and Imaging in Neuroscience

“…ATP and AMP are neuromodulators that regulate numerous neuronal functions in the brain like neurotransmitter synthesis, release, and uptake . During ischemic stroke, ATP depletion occurs due to impaired energy metabolism, leading to neuronal death and brain damage, while AMP levels fluctuate according to the metabolic state of the neurons. , SERS sensors have shown potential for detecting and quantifying ATP with high sensitivity and specificity, with SERS plasmonic core–satellite assemblies and aptamer-conjugated AuNS@Ag detecting ATP levels with an LOD of 0.5 pM . Other studies have also demonstrated label-free detection of ATP in mouse dopaminergic neurons with Au SERS-driven tapered fiber sensors .…”