Inhibition of inflammation by minocycline improves heart failure and depression-like behaviour in rats after myocardial infarction
Wang, Ahmad, Jadayel, Najjar, Lagace, Leenen (2019) Inhibition of inflammation by minocycline improves heart failure and depression-like behaviour in rats after myocardial infarction PLoS One (IF: 3.7) 14(6) e0217437
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Abstract
Patients with heart failure have an increased incidence of depression. Central and peripheral inflammation play a major role in the pathophysiology of both heart failure and depression.Minocycline is an antibiotic that inhibits microglia activation and release of pro-inflammatory cytokines. We assessed effects of minocycline on extent of heart failure and depression at 2 and 8 weeks post myocardial infarction.Male Wistar rats were randomly divided into 3 groups: (i) sham + vehicle; (ii) MI + vehicle; and (iii) MI + minocycline with n/group of 8, 9 and 9 at 2 weeks, and 10, 16, 8 at weeks, respectively. Oral minocycline (50 mg/kg/day) or vehicle started 2 days before surgery. Depression-like behaviour was assessed with sucrose preference and forced swim tests, and cardiac function with echo and hemodynamics. After myocardial infarction, microglia activation and plasma/brain pro-inflammatory cytokines increased, which were mostly prevented by minocycline. At 8 weeks, cardiac dysfunction was attenuated by minocycline: infarct size (MI + Vehicle 29±1, MI + Min 23±1%), ejection fraction (Sham 80±1, MI + Vehicle 48±2, MI + Min 58±2%) and end diastolic pressure (Sham 3.2±0.3, MI + Vehicle 18.2±1.1, MI + Min 8.5±0.9 mm Hg). Depression-like behaviour was significantly improved by minocycline in sucrose preference test (% Sucrose Intake: Sham 96±1, MI + Vehicle 78±2, MI + Min 87±2) and forced swim test (% Immobile: Sham 40±4, MI + Vehicle 61±3, MI + Min 37±6).Rats post myocardial infarction develop systemic inflammation, heart failure and depression-like behaviour that are all attenuated by minocycline. Targeting (neuro) inflammation may represent new therapeutic strategy for patients with heart failure and depression.
Links
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6590948http://www.ncbi.nlm.nih.gov/pubmed/31233508
http://dx.doi.org/10.1371/journal.pone.0217437
