Neuroscience
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The use of antibodies to identify neuronal receptors, neurotransmitters, cytoskeletal elements or pathologic protein aggregates, ion channels, adhesion molecules or other cell-type specific markers, is common practice in neuroscience. Antibody detection systems are often based on confocal, epifluorescence or brightfield microscopy. ⋯ We describe three new settings in which ASE improves the detection of a variety of antibodies applied on long-time stored non-human primate brain sections, cell culture monolayers and on squamous carcinomas retrieved from cervical cancer patients. The significant improvement of ASE over optimized immunohistochemical protocols used in clinical practice (i.e. cancer detection) combined with its simplicity and low cost makes it an attractive method for biomedical applications.
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Dimethyl fumarate (DMF) is the only available approved drug for first line treatment of multiple sclerosis (MS), a lethal condition impairing central nervous system (CNS). To date, however, little is known of its mechanisms of action. Only recently, it has been suggested that DMF exerts neuroprotective effects acting as an immunomodulator and that it may alter the activation state of microglia cells, crucial in MS pathogenesis. ⋯ Here, we examine the effects of DMF treatment on microglia functional activities, as phenotype, morphology, processes motility and rearrangement, migration, ATP response and iron uptake in mouse primary microglia culture and acute hippocampal slices. We found that DMF treatment reduces microglia motility, downregulating functional response to ATP, increases ferritin uptake and pushes microglia towards an anti-inflammatory phenotype, thus reducing its proinflammatory reactivity in response to tissue damage. These results highlight the effects of this compound on microglia functions and provide new insights on the mechanism of action of DMF in MS treatment.
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Differentiation of oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes (OLs) is a key event for axonal myelination in the central nervous system (CNS). Several growth factors and neurotransmitters like GABA are postulated as important regulators of that process, and different protein kinases may also participate in OL differentiation and myelination. However, the molecular mechanisms underlying the regulation of myelination by neurotransmitters are only partially known. ⋯ None of these effects are mediated by the GABAAR agonist muscimol. Together, these results highlight the relevance of the GABAergic system in OL differentiation, and indicate that this functional role is mediated through GABABR involving the participation of Src-family kinases. This article is part of a Special Issue entitled: Honoring Ricardo Miledi - outstanding neuroscientist of XX-XXI centuries.
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Although Ca2+ influx through muscle nAChR-channels has been described over the past 40 years, its functions remain still poorly understood. In this review we suggest possible roles of Ca2+ entry at all stages of muscle development, summarizing the evidence present in literature. nAChRs are expressed in myoblasts prior to fusion, and can be activated in the absence of an ACh-releasing nerve terminal, with Ca2+ influx likely contributing to regulate cell fusion. Upon establishment of nerve-muscle contact, Ca2+ influx contributes to orchestrate the signaling required for the correct formation of the neuromuscular junction. ⋯ However, when genetic defects cause excessive channel activation, Ca2+ influx becomes toxic and causes endplate myopathy. Throughout the review, we highlight how Ricardo Miledi has contributed to construct this whole body of knowledge, from the initial description of Ca2+ permeability of endplate nAChR channels, to the rationale for the treatment of endplate excitotoxic damage under pathological conditions. This article is part of a Special Issue entitled: SI: Honoring Ricardo Miledi - outstanding neuroscientist of XX-XXI centuries.
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Erythropoietin (EPO) is a hematopoietic growth factor that has an important role in the erythropoiesis. EPO and its receptor (EPO-R) are expressed all over in the mammalian brain. Furthermore, it has been reported that EPO may exert neuroprotective effect in animal models of brain disorders as ischemia and epilepsy. ⋯ Our findings show a new modulatory action of EPO on GABAA receptors (GABAA-Rs). This effect could be relevant to balance the GABAergic dysfunction in human TLE. This article is part of a Special Issue entitled: Honoring Ricardo Miledi - outstanding neuroscientist of XX-XXI centuries.