title: 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 µg/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.
authors.affiliation: Department of Physiology, National Defense Medical College, Saitama, Japan Department of Physical Medicine and Rehabilitation, National Defense Medical College, Saitama, Japan.
authors.forename: Risa
authors.initials: R
authors.lastname: Tamura
authors.affiliation: Department of Physiology, National Defense Medical College, Saitama, Japan ohta@ndmc.ac.jp.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ohta
authors.affiliation: Department of Anesthesiology, National Defense Medical College, Saitama, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Satoh
authors.affiliation: Department of Pediatrics, National Defense Medical College, Saitama, Japan.
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Nonoyama
authors.affiliation: Department of Physiology, National Defense Medical College, Saitama, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nishida
authors.affiliation: Department of Psychiatry, National Defense Medical College, Saitama, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Nibuya
mesh_terms: D000243:Adenosine Deaminase / Q000627:therapeutic use*; D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology*; D002540:Cerebral Cortex / Q000473:pathology; D000075402:Channelrhodopsins; D003342:Corpus Striatum / Q000187:drug effects* / Q000473:pathology*; D005071:Evoked Potentials / Q000187:drug effects; D005260:Female; D005947:Glucose / Q000172:deficiency; D002534:Hypoxia, Brain / Q000188:drug therapy / Q000473:pathology; D066298:In Vitro Techniques; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D055647:Rats, Transgenic
chemical_list: D000075402:Channelrhodopsins; D018696:Neuroprotective Agents; D000243:Adenosine Deaminase; D005947:Glucose
keywords: Adenosine; brain ischemia; brain slice; neuroprotection; optogenetics