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A physiological concentration of magnesium (Mg) is essential for optimal skeletal muscle function. Indeed, Mg plays a crucial role during the differentiation process (myogenesis), in muscle fiber composition, muscle contraction and performance. This narrative review describes in detail the relevance of Mg in skeletal muscle, highlighting the importance of adequate Mg intake to ensure optimal skeletal muscle cell function and performance in individuals of all ages. [ABSTRACT FROM AUTHOR]

The article presents the magnesium global network to promote research on magnesium in diseases focusing on covid-19. Topics discussed include this prompted establishment of a worldwide collaborative network with regular virtual meetings to brainstorm the associations between magnesium and COVID-19; and hypothesize that magnesium deficiency, a common but mostly unrecognized state in modern global societies, could be an important component of the susceptibility to SARS-CoV-2 infection.

Purpose: The blood-brain-barrier (BBB), the tight network of endothelial cells in direct contact with astrocytes, isolate the central nervous system (CNS) from the systemic circulation. The integrity of BBB is fundamental to protect the brain from the diffusion of harmful substances but also to guarantee the passage of molecules necessary for the metabolic function. Modifications of BBB's permeability are associated with several neuropathological disorders. The aim of this study was the evaluation of the capability of different endothelial cells in creating a tight barrier in experimental models of BBB and the evaluation of different magnesium salts in modulating BBB performance. Materials and methods: To mimic BBB, HUVEC, a widely used model of macrovascular endothelial cells, or HBMEC, microvascular brain endothelial cells, were co-cultured with astrocytes in transwells. The ability of creating a tight barrier was evaluated both measuring the transendothelial electrical resistance and monitoring the passage of fluorescent molecules from the apical to the basal component of the system. Then the differential expression of the adhesion molecules VE-cadherin and ZO-1 were evaluated in HUVEC and HBMEC. Moreover, the effects of different magnesium salts in modulating these molecules were analyzed. Results: We show that HBMEC create a better barrier than HUVEC, showing a reduced passage of molecules and increased transendothelial electrical resistance. Moreover, the addition of different magnesium salts to the culture medium prevents BBB hyperpermeability induced by LPS and Bradikinin, both known to augment endothelial permeability, by modulating the expression of adhesion molecules. Conclusion: Our results demonstrate that HBMEC should be used in models mimicking BBB. Moreover, the permeability of the BB and the expression of adhesion molecules is modulated by magnesium salts which are beneficial to counteract the increased permeability induced by LPS and Bradykinin. [ABSTRACT FROM AUTHOR]

When Sars-CoV2 began to spread around the globe, some plausible links emerged between the pathophysiology of the infection and magnesium deficiency, which is a common, but often overlooked, finding in apparently healthy people. Initially, we noted that conditions linked to magnesium deficiency in humans, such as aging, diabetes, obesity, hypertension and cardiovascular diseases, are associated with high odds of COVID-19 mortality. Then we reasoned that Mg deficiency might contribute to crucial events in acute COVID-19, such as viral entry in the cells, endothelial dysfunction and cytokine storm. As the population of patients recovering from COVID-19 grows, a low Mg status might have a role in some symptoms of the so-called postacute COVID-19 syndrome, i.e. fatigue, brain fog, joint pain, palpitations, which result a decline in the quality of life and increase frailty. It should be recalled that magnesium deficit determines anxiety, insomnia, hyperemotionality, depression, headache, light-headedness [39], symptoms included in the post-acute COVID-19 syndrome. We conclude that monitoring and restoring magnesium homeostasis through an appropriate nutritional regimen or possibly by supplementation should be regarded as a safe and costeffective intervention that could contribute to prevent SARS-CoV-2 infection, reduce severity of COVID-19 symptoms and facilitate the recovery after the acute phase. [ABSTRACT FROM AUTHOR]

Purpose: Mini-brain organoids 3D model represent a unique model to study neurobiology and neuropathology. Since magnesium protects against neuroinflammation and neurodegeneration, we evaluated the effects of different concentration of magnesium (Mg) salts (MgSulphate and MgPidolate) on human mini-brain organoids in the presence or not of an in vitro generated blood brain barrier (BBB). Indeed, we have previously shown that the BBB is differently permeable to distinct Mg salts. We focused on BDNF and GABA-receptors, both involved in neurodegeneration and neuroregeneration. Materials and methods: The brain-organoids were generated from human induced Pluripotent Stem cells and differentiated for 30 days. The organoids, alone or in the presence of BBB, were treated with different concentrations of MgSulphate and MgPidolate for 5 days. The expression of different neurological markers was evaluated by Real Time PCRs. The structure of organoids was evaluated by hematoxylin eosin staining and neurological markers by immuno- fluorescence. Results: Our data show that the presence of the BBB influences the expression of BDNF and GABAR in mini-brain. Indeed, high concentration of MgPidolate (5mM) upregulates only the GABAB-r when organoids are cultured without BBB. On the contrary, in the presence of BBB, a significant upregulation of BDNF and GABAR was induced by 5mM MgPidolate. No differences in the structures of organoids were detected by hematoxylin eosin staining and immunofluorescence. Conclusion: This study demonstrates that the presence of the BBB selectively changes BDNF and GABAR expression in mini-brain exposed to high concentration of MgPidolate. Because BDNF and the GABAergic system are involved in critical CNS functions, ranging from neuronal development and neuronal survival to learning and memory, these results might illuminate novel pathways explaining the neuroprotective effect of Mg. [ABSTRACT FROM AUTHOR]