Neuroprotective effects of adenosine deaminase in the striatum

Abstract

Adenosine deaminase (ADA) is a ubiquitous enzyme that catabolizes adenosine and deoxyadenosine. During cerebral ischemia, extracellular adenosine levels increase acutely and adenosine deaminase catabolizes the increased levels of adenosine. Since adenosine is a known neuroprotective agent, adenosine deaminase was thought to have a negative effect during ischemia. In this study, however, we demonstrate that adenosine deaminase has substantial neuroprotective effects in the striatum, which is especially vulnerable during cerebral ischemia. We used temporary oxygen/glucose deprivation (OGD) to simulate ischemia in rat corticostriatal brain slices. We used field potentials as the primary measure of neuronal damage. For stable and efficient electrophysiological assessment, we used transgenic rats expressing channelrhodopsin-2, which depolarizes neurons in response to blue light. Time courses of electrically evoked striatal field potential (eFP) and optogenetically evoked striatal field potential (optFP) were recorded during and after oxygen/glucose deprivation. The levels of both eFP and optFP decreased after 10 min of oxygen/glucose deprivation. Bath-application of 10 mg/ml adenosine deaminase during oxygen/glucose deprivation significantly attenuated the oxygen/glucose deprivation-induced reduction in levels of eFP and optFP. The number of injured cells decreased significantly, and western blot analysis indicated a significant decrease of autophagic signaling in the adenosine deaminase-treated oxygen/glucose deprivation slices. These results indicate that adenosine deaminase has protective effects in the striatum.

Erythropoietin, a putative neurotransmitter during hypoxia, is produced in RVLM neurons and activates them in neonatal Wistar rats

“…In this experiment, we referred to a method used in previous reports. To create an ischemic condition, Tamura et al ( 26 ) exposed adult rat corticostriatal brain slices to 30 min of hypoxia (N 2 95%-CO 2 5%) with temporary oxygen/glucose deprivation. Then, after 1 h of oxygenated (95% O 2 -5% CO 2 ) incubation with aCSF, they found that the protein expression of light chain 3-II had increased more in the ischemia group than in the control group.…”

“…After the 30 - min treatment, the sections in both groups were oxygenated with 5% CO 2 -95% O 2 for 3 h at room temperature (23°C ± 1°C) (see Fig. 6 B ) ( 26 ).…”

Research progress on adenosine in central nervous system diseases

“…There are two main metabolic pathways of adenosine: (a) it becomes inosine under the action of adenosine deaminase (ADA) then generates hypoxanthine and hypoxanthine nucleotides through nucleosidases and finally becomes uric acid, which is an end product of purine derivatives in human metabolism . (b) Most adenosine enters the cell via a bidirectional balance transporter, and the adenosine kinase (ADK), which generates AMP by phosphorylation in central cells, only exists in the astrocytes.…”

Dynamics of Markers of the Functional State of Erythrocytes as a Reaction of Patients with Surgical Aortic Pathology to Surgical Intervention using Cardiopulmonary Bypass

“…У тканинах гемоглобін залишає необхідний для дихання газ, замінюючи його вже відпрацьованим вуглекислим газом, і відносить назад до легеневих альвеол. Виведення гемоглобіном вуглекислоти дозволяє знижувати рівень кислотності в організмі, тим самим, підтримуючи рівновагу pH і виконуючи функцію регулятора [9,10].…”