Brain-derived neurotrophic factor(The Max Planck Institute)

Atrial fibrillation is the most common arrhythmia worldwide and is associated with significant morbidity and mortality. Despite the effectiveness of catheter-based ablation, periprocedural complication and recurrences remain a concern. In this context, we aim to appraise the potential impact of brain-derived neurotrophic factor (BDNF) on reducing episodes of paroxysmal atrial fibrillation (PAF).

22 patients with an established diagnosis of PAF and without structural heart disease were considered. Every patient received 20 drops of GUNA-BDNF administered in the morning. During the 24 months of follow-up, the arrhythmic burden was measured by the average monthly duration of PAF episodes.

At the end of the follow-up period (24 months), data from 22 patients, of whom 17 men and five women, were analyzed. The arrhythmic burden, measured in terms of average monthly duration of PAF episodes, was found significantly reduced after the administration of low dose BDNF (9.5 vs. 65.3 minutes per month, P<0.001). A total of 17 out of 22 patients saw their arrhythmic burden eliminated or consistently reduced, furthermore two patients underwent a drastic reduction of the average monthly duration of AF (more than 200 minutes compared to the baseline). Only four patients, despite the administration of BDNF, still experienced an arrhythmic burden of 20 minutes or more. Considering the age groups, the major reduction was observed in people aged 70 or more, who were also the most represented in the sample. These results are coherent with the poor literature currently available.

BDNF low dose therapy has shown to have an impacting role in reducing the arrhythmic burden and recurrences of AF, with a particular effectiveness in patients over 70 and without structural heart disease. We should welcome this work, despite it limitations. Further clinical and molecular studies are needed before-considering BDNF low dose as a tool against PAF.

Exercise reduces cognitive aging, neurodegeneration, and Alzheimer's disease (AD) risk. Acute exercise reduces the activity of β-site amyloid precursor protein-cleaving enzyme 1 (BACE1), the rate-limiting enzyme in the production of Aβ. However, mechanisms mediating these effects remain largely unknown. Work has implicated brain-derived neurotrophic factor (BDNF) in the processing of amyloid precursor protein (APP). BDNF is an exercise-induced neurotrophin known for its role in synaptic plasticity, neurite growth, and neuronal survival. Previously, our lab has shown using an ex vivo model that treatment of the prefrontal cortex with BDNF reduced BACE1 activity, highlighting a BDNF to BACE1 link. The purpose of this research was to examine whether BDNF treatments resulted in similar biochemical adaptations to APP processing as exercise training. Male C57BL6/J mice were assigned into one of four groups (n = 12/group): 1) control; 2) exercise training (progressive treadmill training 5 days/wk); 3) BDNF (0.5 mg/kg body mass subcutaneous injection 5 days/wk); or 4) endurance training and BDNF, for an 8-wk intervention. Recognition memory was measured with a novel object recognition test. Serum, the prefrontal cortex, and hippocampus were collected. BDNF improved recognition memory to a similar extent as endurance training. BDNF and exercise decreased BACE1 activity and increased ADAM10 activity in the prefrontal cortex, indicating a shift in APP processing. Our novel results indicate that BDNF exerts similar beneficial effects on cognition and APP processing as exercise training. Future evidence-based preventative or therapeutic interventions that increase BDNF and reduce BACE1 will be of value for populations that are at risk of AD.NEW & NOTEWORTHY Our study presents the novel findings that chronic peripheral BDNF injections result in regulation of APP processing enzymes and improved cognition to a similar extent as exercise training. These findings highlight the potential efficacy of using BDNF as a therapeutic intervention in the prevention of neurodegenerative diseases (i.e., Alzheimer's disease). Furthermore, future evidence-based preventative or therapeutic interventions that increase BDNF and reduce BACE1 will be of value for populations that are at risk of AD.