Myocardial brain-derived neurotrophic factor regulates cardiac bioenergetics through the transcription factor Yin Yang 1.

AIMS: Brain-derived neurotrophic factor (BDNF) is markedly decreased in heart failure patients. Both BDNF and its receptor, tropomyosin-related kinase receptor (TrkB), are expressed in cardiomyocytes; however, the role of myocardial BDNF signalling in cardiac pathophysiology is poorly understood. Here, we investigated the role of BDNF/TrkB signalling in cardiac stress response to exercise and pathological stress. METHODS AND RESULTS: We found that myocardial BDNF expression was increased in mice with swimming exercise but decreased in a mouse heart failure model and human failing hearts. Cardiac-specific TrkB knockout (cTrkB KO) mice displayed a blunted adaptive cardiac response to exercise, with attenuated upregulation of transcription factor networks controlling mitochondrial biogenesis/metabolism, including peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α). In response to pathological stress (transaortic constriction, TAC), cTrkB KO mice showed an exacerbated heart failure progression. The downregulation of PGC-1α in cTrkB KO mice exposed to exercise or TAC resulted in decreased cardiac energetics. We further unravelled that BDNF induces PGC-1α upregulation and bioenergetics through a novel signalling pathway, the pleiotropic transcription factor Yin Yang 1. CONCLUSION: Taken together, our findings suggest that myocardial BDNF plays a critical role in regulating cellular energetics in the cardiac stress response.

Analysis of organochlorine pesticides residues in fish from Edko Lake (North of Egypt) using eco-friendly method and their health implications for humans.

Levels of organochlorine pesticides (OCPs) residues in tilapia fish and their health risk associated with the consumption of fish from Edko lake, Egypt were determined. The quick, easy, cheap, effective, rugged, and safe method (QuEChERS) was used for extraction and clean-up of 18 OCPs residues from fish followed by GC-ECD and GC-ITD analytical tools were employed for identification of OPs. Out of the 18 OCPs, only heptachlorepoxide, p,p-DDE, dieldrin, p,p-DDD, and endrin ketone were detected in muscles of fish with concentrations of 0.1144, 0.2119, 0.4352, 0.1196, and 0.1323 µg/Kg bw, respectively. Results of the risk assessment calculations showed that dieldrin had a health risk index of more than one. This means that there was a health risk to adults associated with the consumption of fish. On the other hand, heptachlorepoxide, p,p-DDE, p,p-DDD, and endrin ketone did not show any direct health risk. Contamination of fish, collected from Edko lake in Egypt, with residues of OCPs might pose health implications if fish were consumed fresh. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s43188-020-00085-8.