Elsevier

Biological Psychiatry

Volume 59, Issue 5, 1 March 2006, Pages 430-433
Biological Psychiatry

Original article
Apoptosis Detected in the Amygdala Following Myocardial Infarction in the Rat

https://doi.org/10.1016/j.biopsych.2005.07.018Get rights and content

Background

Myocardial infarction (MI) contains a risk factor for developing episodes of Major Depressive Disorder (MDD). Apoptosis is commonly observed in the reperfused myocardial infarcted heart, and recent findings sugges the existence of apoptosis in MDD. Cytokines, which are released by ischemic myocardium and which may induce apoptosis, have been proposed as a possible cause for MDD.

Methods

Myocardial infarction was produced in anesthetized rats by a 40-minute occlusion of the left anterior descending coronary artery followed by 72 hours of reperfusion. Determination of apoptosis was done in the amygdala, hippocampus and vermis of MI and Sham rats treated or not with pentoxyfilline (PTX), a cytokine synthesis inhibitor (10 mg/kg/day intraperitoneal).

Results

Compared to Sham rats, the amygdala of MI rats showed significantly reduced P13K activity, increased Bax/Bcl-2 ratio, caspase-3 activity, and TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling)-positive cells. The effect of MI on apoptosis was completely reversed in presence of PTX. No statistical difference was observed in the hippocampus and the vermis in the different groups for any of the biochemical measurements.

Conclusions

These results indicated that MI induce apoptosis in amygdala by a cytokine-sensitive mechanism and may explain the MDD observed following myocardial infarction.

Section snippets

Methods and Materials

Forty-seven Sprague–Dawley rats (Charles River Canada, Saint-Constant, Québec) weighing 300–350 g were included in this study. All procedures were in accordance with the rules of the Canadian Council on Animal Care.

Infarct Size

In our experimental model, infarct size in the MI group was 54% ± 2% of the area at risk (n = 17) and 50% ± 2% for the MI+PTX group (n = 9; p = .2059 vs. MI only). The area at risk represents around 50% of left ventricle. Number of Sham rats was 14 and 7 for the Sham + PTX.

PI3K Activity

Activity of PI3K observed in the amygdala was significantly decreased in the MI group (36% ± 10%) as compared with the Sham group (Figure 1A). This effect is completely blocked in MI+PTX group (3.6% ± 3.4% of Sham). No

Discussion

The amygdala is a key component of the limbic system and has been associated with emotional, motivational, and homeostatic components of MDD (Nieuwenhuys 1996). The amygdala maintains connections with other brain areas, including the hippocampus, thalamus, neocortex, striatum, and basal forebrain. The amygdala is also involved in the regulation of cardiovascular functions mainly by modulation of neuronal activity including the autonomic parasympathetic level and the baroreceptor reflex arc (Ter

References (13)

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