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Apoptosis

, Volume 11, Issue 7, pp 1067–1074 | Cite as

Reduction of apoptosis in the amygdala by an A2A adenosine receptor agonist following myocardial infarction

  • M. Boucher
  • B. P. Wann
  • S. Kaloustian
  • R. Cardinal
  • R. Godbout
  • G. Rousseau
Reports

Abstract

It has been observed that a cytokine synthesis inhibitor, pentoxifylline, prevents the apoptotic processes taking place in the amygdala following myocardial infarction. However, it is unknown if the cardioprotective effect of A2A adenosine receptor agonist, CGS21680, which reduces cytokine synthesis, would lead to such amygdala apoptosis regression. Thus, this study was designed to investigate whether cardioprotective A2A adenosine receptor activation reduces apoptosis in the amygdala following myocardial infarction. Anesthetized rats were subjected to left anterior descending coronary artery occlusion for 40 min, followed by 72 h of reperfusion. The A2A agonist CGS21680 (0.2 μg/kg/min i.v.) was administered continuously for 120 min, starting (1) five minutes prior to instituting reperfusion (Early) or (2) five minutes after the beginning of reperfusion (Late). After reperfusion, myocardial infarct size was determined and the amygdala was dissected from the brain. Infarct size was reduced significantly in the Early compared to the Control group (34.6 ± 1.8% and 52.3 ± 2.8% respectively; p < 0.05), with no difference com-pared to the Late group (40.1 ± 6.1%). Apoptosis regressi-on was documented in the amygdala of the Early group by an enhanced phosphatidylinositol 3-kinase-Akt pathway activation and Bcl-2 expression concurrently to a caspase-3 activation limitation and reduction in TUNEL-positive cells staining. On the other hand, amygdala TUNEL-positive cell numbers were not reduced in the Late group. Moreover, TNFα was significantly reduced in the amygdala of the Early group compared to the Control and Late groups. These results indicate that A2A adenosine receptor stimulation is associated with apoptosis regression in the amygdala following myocardial infarction.

Keywords

A2A adenosine receptors amygdala cardioprotection inflammation myocardial infarction reperfusion 

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Copyright information

© Springer Science + Business Media, LLC 2006

Authors and Affiliations

  • M. Boucher
    • 1
    • 2
  • B. P. Wann
    • 1
    • 3
  • S. Kaloustian
    • 1
    • 2
  • R. Cardinal
    • 1
    • 2
  • R. Godbout
    • 1
    • 3
  • G. Rousseau
    • 1
    • 2
    • 4
  1. 1.Centre de Biomédecine, Hôpital du Sacré-Coeur de MontréalMontréal, (Québec)Canada
  2. 2.Département de PharmacologieMontréalCanada
  3. 3.Département de Psychiatrie, Faculté de MédecineUniversité de MontréalMontréalCanada
  4. 4.Ph.D., Centre de Biomédecine, Hôpital du Sacré-Coeur de MontréalMontréalCanada

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