Correlation of transient adenosine release and oxygen changes in the caudate‐putamen

Abstract

Adenosine is an endogenous nucleoside that modulates important physiological processes, such as vasodilation, in the central nervous system. A rapid, 2–4 seconds, mode of adenosine signaling has been recently discovered, but the relationship between this type of adenosine and blood flow change has not been characterized. In this study, adenosine and oxygen changes were simultaneously measured using fast-scan cyclic voltammetry. Oxygen changes occur when there is an increase in local cerebral blood flow and thus are a measure of vasodilation. About 34% of adenosine transients in the rat caudate-putamen are correlated with a subsequent transient change in oxygen. The amount of oxygen was correlated with the concentration of adenosine release and larger adenosine transients (over 0.4 μM) always had subsequent oxygen changes. The average duration of adenosine and oxygen transients were 3.2 seconds and 3.5 seconds, respectively. On average, the adenosine release starts and peaks 0.2 seconds prior to the oxygen. The A2a antagonist, SCH442416, decreased the number of both adenosine and oxygen transient events by about 32%. However, the A1 antagonist, DPCPX, did not significantly affect simultaneous adenosine and oxygen release. The nitric oxide (NO) synthase inhibitor L-NAME also did not affect the concentration or number of adenosine and oxygen release events. These results demonstrate that both adenosine and oxygen release are modulated via A2a receptors. The correlation of transient concentrations, time delay between adenosine and oxygen peaks, and effect of A2a receptors suggests adenosine modulates blood flow on a rapid, sub-second time scale.

Analytical Techniques in Neuroscience: Recent Advances in Imaging, Separation, and Electrochemical Methods

“…More recently, we developed an FSCV adenosine/oxygen waveform to detect adenosine and oxygen changes simultaneously in vivo in the rat caudate-putamen. 181 This study modified previous waveforms that had extended the anodic limits to −1.4 V to detect oxygen reduction and dopamine oxidation. 182 For adenosine and oxygen, the electrode was scanned from 0 V to +1.45 V, then to −1.4 V and back to 0 V every 100 millseconds at a scan rate of 450 V/s.…”

Automated Algorithm for Detection of Transient Adenosine Release

“…Another possible extension is to look for multiple analytes in the same data. Adenosine and oxygen release events are correlated, 27 so the program could scan the reduction voltage for oxygen and identify oxygen transients that occurs after an adenosine transient. Thus, as long as there is enough information to make rules about detection from the electrochemical data, this modular program can be used to automatically pick peaks and characterize them.…”

Automated algorithm for measurement of spontaneous adenosine transients in large electrochemical data sets

“…The combination of principal components analysis with inverse least-squares regression is known as principal components regression (PCR) 25 .…”

“…exceeds the threshold value in a training set (Q α ) then a source of variation is not accounted for in the PCA model and the value should be retained 25,26 . An example of PCR can be observed in Figure 1.5 for dopamine and pH.…”

“…Moreover, the strategy for detecting adenosine transients could be extended to other analytes like oxygen and dopamine. For instance, oxygen and adenosine release are correlated, so the program could scan the reduction voltage for oxygen in a window after an adenosine peak is detected to scan for oxygen transients 25 . Additionally, the algorithm could scan oxidation and reduction voltages for dopamine, with the time-lag threshold set to zero, and automatically detect spontaneous dopamine transients.…”