title: Mechanical stimulation evokes rapid increases in extracellular adenosine concentration in the prefrontal cortex.
abstract: Mechanical perturbations can release ATP, which is broken down to adenosine. In this work, we used carbon-fiber microelectrodes and fast-scan cyclic voltammetry to measure mechanically stimulated adenosine in the brain by lowering the electrode 50 μm. Mechanical stimulation evoked adenosine in vivo (average: 3.3 ± 0.6 μM) and in brain slices (average: 0.8 ± 0.1 μM) in the prefrontal cortex. The release was transient, lasting 18 ± 2 s. Lowering a 15-μm-diameter glass pipette near the carbon-fiber microelectrode produced similar results as lowering the actual microelectrode. However, applying a small puff of artificial cerebral spinal fluid was not sufficient to evoke adenosine. Multiple stimulations within a 50-μm region of a slice did not significantly change over time or damage cells. Chelating calcium with EDTA or blocking sodium channels with tetrodotoxin significantly decreased mechanically evoked adenosine, signifying that the release is activity dependent. An alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione, did not affect mechanically stimulated adenosine; however, the nucleoside triphosphate diphosphohydrolase 1,2 and 3 (NTDPase) inhibitor POM-1 significantly reduced adenosine so a portion of adenosine is dependent on extracellular ATP metabolism. Thus, mechanical perturbations from inserting a probe in the brain cause rapid, transient adenosine signaling which might be neuroprotective. We have discovered immediate changes in adenosine concentration in the prefrontal cortex following mechanical stimulation. The adenosine increase lasts only about 20 s. Mechanically stimulated adenosine was activity dependent and mostly because of extracellular ATP metabolism. This rapid, transient increase in adenosine may help protect tissue and would occur during implantation of any electrode, such as during deep brain stimulation.
authors.affiliation: Department of Chemistry, University of Virginia, Charlottesville, Virginia, USA.
authors.forename: Ashley E
authors.initials: AE
authors.lastname: Ross
authors.forename: Michael D
authors.initials: MD
authors.lastname: Nguyen
authors.forename: Eve
authors.initials: E
authors.lastname: Privman
authors.forename: B Jill
authors.initials: BJ
authors.lastname: Venton
mesh_terms: D000241:Adenosine / Q000096:biosynthesis* / Q000378:metabolism*; D000818:Animals; D004558:Electric Stimulation / Q000379:methods; D004567:Electrodes, Implanted; D045604:Extracellular Fluid / Q000378:metabolism*; D008297:Male; D008839:Microelectrodes; D009924:Organ Culture Techniques; D010812:Physical Stimulation / Q000379:methods; D017397:Prefrontal Cortex / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000502:physiology*
chemical_list: D000241:Adenosine
keywords: ATP; adenosine; fast-scan cyclic voltammetry; mechanical stimulation; prefrontal cortex; sensor