Purine level regulation during energy depletion associated with graded excitatory stimulation in brain

P. Nickolas Shepel, David Ramonet, Patrick Stevens, Jonathan D. Geiger

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

Objectives: The formation and release of adenosine following graded excitatory stimulation of the brain may serve important physiological functions such as sleep regulation, as well as an early resistance mechanism against excitotoxicity. However, adenosine at high levels may reflect merely the results of obstructed energy metabolism. Methods: We examined the extent to which levels of adenosine and adenylate energy charge are affected in vivo by graded excitatory stimulations of brain using unilateral intrastriatal injections of glutamatergic agents and head-focused high energy microwaving for accurate and precise measures of purines. Results: Our results confirmed that adenosine levels rise when adenylate energy charge decreases and showed that these increases occurred in three distinct phases with the rate of adenosine formation in each phase increasing as tissue adenylate energy charge was further depleted. In addition, we observed that, in most cases, the effects of focal excitatory stimulation on changes in tissue purine levels were restricted spatially within the immediate vicinity of the injection site; however, when strongly depolarizing stimuli were used, changes in purine levels could be observed in adjacent and, occasionally, even in contralateral brain regions. Discussion: These results provide new insight into purine regulation that occurs under physiologically relevant conditions, such as sleep and during the early stages of brain insults that induce excitotoxicity.

Original languageEnglish (US)
Pages (from-to)139-148
Number of pages10
JournalNeurological research
Volume27
Issue number2
DOIs
StatePublished - Mar 1 2005

    Fingerprint

Keywords

  • ATP
  • Adenosine
  • Adenylate energy charge
  • Glutamate
  • Microwave irradiation

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this