Testosterone replacement attenuates cognitive decline in testosterone-deprived lean rats,but not in obese rats,by mitigating brain oxidative stress

Testosterone replacement improves metabolic parameters and cognitive function in hypogonadism. However, the effects of testosterone therapy on cognition in obese condition with testosterone deprivation have not been investigated. We hypothesized that testosterone replacement improves cognitive function in testosterone-deprived obese rats by restoring brain insulin sensitivity, brain mitochondrial function, and hippocampal synaptic plasticity. Thirty male Wistar rats had either a bilateral orchiectomy (ORX: O, n = 24) or a sham operation (S, n = 6). ORX rats were further divided into two groups fed with either a normal diet (NDO) or a high-fat diet (HFO) for 12 weeks. Then, ORX rats in each dietary group were divided into two subgroups (n = 6/subgroup) and were given either castor oil or testosterone (2 mg/kg/day, s.c.) for 4 weeks. At the end of this protocol, cognitive function, metabolic parameters, brain insulin sensitivity, hippocampal synaptic plasticity, and brain mitochondrial function were determined. We found that testosterone replacement increased peripheral insulin sensitivity, decreased circulation and brain oxidative stress levels, and attenuated brain mitochondrial ROS production in HFO rats. However, testosterone failed to restore hippocampal synaptic plasticity and cognitive function in HFO rats. In contrast, in NDO rats, testosterone decreased circulation and brain oxidative stress levels, attenuated brain mitochondrial ROS production, and restored hippocampal synaptic plasticity as well as cognitive function. These findings suggest that testosterone replacement improved peripheral insulin sensitivity and decreased oxidative stress levels, but failed to restore hippocampal synaptic plasticity and cognitive function in testosterone-deprived obese rats. However, it provided beneficial effects in reversing cognitive impairment in testosterone-deprived non-obese rats.     

Termination of spiral waves during cardiac fibrillation via shock-induced phase resetting

Multiple unstable spiral waves rotating around phase singularities (PSs) in the heart, i.e., ventricular fibrillation (VF), is the leading cause of death in the industrialized world. Spiral waves are ubiquitous in nature and have been extensively studied by physiologists, mathematicians, chemists, and biologists, with particular emphasis on their movement and stability. Spiral waves are not easy to terminate because of the difficulty of “breaking” the continuous spatial progression of phase around the PSs. The only means to stop VF (i.e., cardiac defibrillation) is to deliver a strong electric shock to the heart. Here, we use the similarities between spiral wave dynamics and limit cycle oscillators to characterize the spatio-temporal dynamics of VF and defibrillation via phase-resetting curves. During VF, only PSs, including their formation and termination, were associated with large phase changes. At low shock strengths, phase-resetting curves exhibited characteristics of weak (type 1) resetting. As shock strength increased, the number of postshock PSs decreased to zero coincident with a transition to strong (type 0) resetting. Our results indicate that shock-induced spiral wave termination in the heart is caused by altering the phase around the PSs, such that, depending on the preshock phase, sites are either excited by membrane depolarization (phase advanced) or exhibit slowed membrane repolarization (phase delay). Strong shocks that defibrillate break the continuity of phase around PSs by forcing the state of all sites to the fast portion of state space, thus quickly leading to a “homogeneity of state,” subsequent global repolarization and spiral wave termination.     

The effects of acetylcholinesterase inhibitors on the heart in acute myocardial infarction and heart failure: From cells to patient reports

Cardiovascular diseases remain a major cause of morbidity and mortality worldwide. Cardiovascular diseases such as acute myocardial infarction, ischaemia/reperfusion injury and heart failure are associated with cardiac autonomic imbalance characterized by sympathetic overactivity and parasympathetic withdrawal from the heart. Increased parasympathetic activity by electrical vagal nerve stimulation has been shown to provide beneficial effects in the case of cardiovascular diseases in both animals and patients by improving autonomic function, cardiac remodelling and mitochondrial function. However, clinical limitations for electrical vagal nerve stimulation exist because of its invasive nature, costly equipment and limited clinical validation. Therefore, novel therapeutic approaches which moderate parasympathetic activities could be beneficial for in the case of cardiovascular disease. Acetylcholinesterase inhibitors inhibit acetylcholinesterase and hence increase cholinergic transmission. Recent studies have reported that acetylcholinesterase inhibitors improve autonomic function and cardiac function in cardiovascular disease models. Despite its potential clinical benefits for cardiovascular disease patients, the role of acetylcholinesterase inhibitors in acute myocardial infarction and heart failure remediation remains unclear. This article comprehensively reviews the effects of acetylcholinesterase inhibitors on the heart in acute myocardial infarction and heart failure scenarios from in vitro and in vivo studies to clinical reports. The mechanisms involved are also discussed in this review.     

Chronic treatment with prebiotics,probiotics and synbiotics attenuated cardiac dysfunction by improving cardiac mitochondrial dysfunction in male obese insulin-resistant rats

European Journal of Nutrition - In metabolic syndrome, the composition of gut microbiota has been disrupted, and is associated with left ventricular (LV) dysfunction. Several types of prebiotics,...     

An apoptosis inhibitor suppresses microglial and astrocytic activation after cardiac ischemia/reperfusion injury

Inflammation Research - Microglial hyperactivation and apoptosis were observed following myocardial infarction and ischemia reperfusion (I/R) injury. This study aimed to test the hypothesis that...