RESUMO
Multiple Sclerosis (MS) is a chronic disease characterized by immune-mediated destruction of myelinating oligodendroglia in the central nervous system. Loss of myelin leads to neurological dysfunction and, if myelin repair fails, neurodegeneration of the denuded axons. Virtually all treatments for MS act by suppressing immune function, but do not alter myelin repair outcomes or long-term disability. Excitingly, the diabetes drug metformin, a potent activator of the cellular "energy sensor" AMPK complex, has recently been reported to enhance recovery from demyelination. In aged mice, metformin can restore responsiveness of oligodendrocyte progenitor cells (OPCs) to pro-differentiation cues, enhancing their ability to differentiate and thus repair myelin. However, metformin's influence on young oligodendroglia remains poorly understood. Here we investigated metformin's effect on the temporal dynamics of differentiation and metabolism in young, healthy oligodendroglia and in oligodendroglia following myelin damage in young adult mice. Our findings reveal that metformin accelerates early stages of myelin repair following cuprizone-induced myelin damage. Metformin treatment of both isolated OPCs and oligodendrocytes altered cellular bioenergetics, but in distinct ways, suppressing oxidative phosphorylation and enhancing glycolysis in OPCs, but enhancing oxidative phosphorylation and glycolysis in both immature and mature oligodendrocytes. In addition, metformin accelerated the differentiation of OPCs to oligodendrocytes in an AMPK-dependent manner that was also dependent on metformin's ability to modulate cell metabolism. In summary, metformin dramatically alters metabolism and accelerates oligodendroglial differentiation both in health and following myelin damage. This finding broadens our knowledge of metformin's potential to promote myelin repair in MS and in other diseases with myelin loss or altered myelination dynamics.
RESUMO
Once believed to be part of the nervenkitt or "nerve glue" network in the central nervous system (CNS), oligodendroglial cells now have established roles in key neurological functions such as myelination, neuroprotection, and motor learning. More recently, oligodendroglia has become the subject of intense investigations aimed at understanding the contributions of its energetics to CNS physiology and pathology. In this review, we discuss the current understanding of oligodendroglial metabolism in regulating key stages of oligodendroglial development and health, its role in providing energy to neighboring cells such as neurons, as well as how alterations in oligodendroglial bioenergetics contribute to disease states. Importantly, we highlight how certain inputs can regulate oligodendroglial metabolism, including extrinsic and intrinsic mediators of cellular signaling, pharmacological compounds, and even dietary interventions. Lastly, we discuss emerging studies aimed at discovering the therapeutic potential of targeting components within oligodendroglial bioenergetic pathways.
RESUMO
Candida albicans is an opportunistic pathogen which can lead to Candidiasis and blood-stream infections, resulting in a mortality rate near 40%. Given its high fatality and emerging pathogenicity, there is a strong need for the development of a rapid C. albicans diagnostic assay. Point-of-care devices, specifically lateral flow assays, are an attractive and often employed diagnostic modality for C. albicans detection. However, they lack the required performance characteristics needed for accurate pathogen detection and subsequent treatment options. Thus, we describe herein the utility of the Dual Path Platform (DPP®) device as an immunochromatographic Point-of-care assay for C. albicans. The limit of detection for hyphal and budding C. albicans in DPP® tests are reported to be as low as 7.94 × 10(5) whole cells/mL in human serum. C. albicans cells were detected with up to a 3.9 fold increase in sensitivity on DPP® when compared to conventional lateral flow modalities.