Exercise promotes learning and memory formation. These effects depend on increases in hippocampal BDNF, a growth factor associated with cognitive improvement and the alleviation of depression symptoms. Identifying molecules that are produced during exercise and that mediate hippocampal Bdnf expression will allow us to harness the therapeutic potential of exercise. Here, we report that an endogenous molecule produced during exercise in male mice induces the Mus musculus Bdnf gene and promotes learning and memory formation. The metabolite lactate, which is released during exercise by the muscles, crosses the blood-brain barrier and induces Bdnf expression and TRKB signaling in the hippocampus. Indeed, we find that lactate-dependent increases in BDNF are associated with improved spatial learning and memory retention. The action of lactate is dependent on the activation of the Sirtuin1 deacetylase. SIRT1 increases the levels of the transcriptional coactivator PGC1a and the secreted molecule FNDC5, known to mediate Bdnf expression. These results reveal an endogenous mechanism to explain how physical exercise leads to the induction of BDNF, and identify lactate as a potential endogenous molecule that may have therapeutic value for CNS diseases in which BDNF signaling is disrupted.It is established that exercise promotes learning and memory formation and alleviates the symptoms of depression. These effects are mediated through inducing Bdnf expression and signaling in the hippocampus. Understanding how exercise induces Bdnf and identifying the molecules that mediate this induction will allow us to design therapeutic strategies that can mimic the effects of exercise on the brain, especially for patients with CNS disorders characterized by a decrease in Bdnf expression and who cannot exercise because of their conditions. We identify lactate as an endogenous metabolite that is produced during exercise, crosses the blood-brain barrier and promotes hippocampal dependent learning and memory in a BDNF-dependent manner. Our work identifies lactate as a component of the "exercise pill."
Objective: Since the emergence of the COVID-19 pandemic at the end of 2019, the number of affected cases has not stopped rising. Similarly, the number of scientific publications and pre-prints has been increasing exponentially, with an effort to understand this disease more and find a proper solution. The purpose of this article is to review the current understanding of the novel coronavirus. Background: The latest COVID-19 pandemic caused by the SARS-CoV-2 has spread globally ever since it emerged in Wuhan's city in China. This rapidly spreading disease has changed our lives in unimaginable ways, spreading fear and uncertainty due to the lack of knowledge and the flooding with new information, which lacks the scientific method and cannot be critically appraised. The purpose of this article is to gather some of the best knowledge that has been published so far in a unified narrative review, making it easy for the scientific community to review the most accurate and recent understandings about COVID-19. Methods: We screened relevant articles using a specified number of keywords and specific databases, including PubMed and Embase. We selected peer-reviewed English published material related to the topic, except for a few pre-prints that we deemed necessary to include. We also screened the reference lists of these articles to find relevant publications with the same criteria. Discussion: This narrative overview comprises several subsections that discuss the epidemiology, virology, pathogenesis, clinical manifestations, diagnostic methods, and management of the disease. We also presented a section on the implications of the disease in pregnancy. We wrapped up the review with a special division regarding the response to COVID-19, which has been diverse in different countries. Conclusion: COVID-19 has been a serious global health threat with a high transmission and case fatality rate, particularly in vulnerable populations. Epidemiologic models have so far guided the response, but they need to be interpreted carefully, with an understanding of their limitations. The disease's response has varied among different countries; with no current vaccine or standard treatment, the world stands in fear, maximizing preventive strategies to reduce the damages caused by this virus. This manuscript presents a summary of everything that is so far known about COVID-19 to make it easier for the medical community to overview the disease that has changed the world.
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