RESUMO
Inflammatory demyelinating diseases (IDDs) are among the main causes of inflammatory and neurodegenerative injury of the central nervous system (CNS) in young adult patients. Of these, multiple sclerosis (MS) is the most frequent and studied, as it affects about a million people in the USA alone. The understanding of the mechanisms underlying their pathology has been advancing, although there are still no highly effective disease-modifying treatments for the progressive symptoms and disability in the late stages of disease. Among these mechanisms, the action of glial cells upon lesion and regeneration has become a prominent research topic, helped not only by the discovery of glia as targets of autoantibodies, but also by their role on CNS homeostasis and neuroinflammation. In the present article, we discuss the participation of glial cells in IDDs, as well as their association with demyelination and synaptic dysfunction throughout the course of the disease and in experimental models, with a focus on MS phenotypes. Further, we discuss the involvement of microglia and astrocytes in lesion formation and organization, remyelination, synaptic induction and pruning through different signaling pathways. We argue that evidence of the several glia-mediated mechanisms in the course of CNS demyelinating diseases supports glial cells as viable targets for therapy development.
Assuntos
Doenças do Sistema Nervoso Central , Esclerose Múltipla , Humanos , Neuroglia , Doenças do Sistema Nervoso Central/metabolismo , Esclerose Múltipla/metabolismo , Sistema Nervoso Central , Microglia/metabolismoRESUMO
Alzheimer's disease (AD) and other forms of dementia was ranked 3rd in both the Americas and Europe in 2019 in a World Health Organization (WHO) publication listing the leading causes of death and disability worldwide. Copper (Cu) imbalance has been reported in AD and increasing evidence suggests metal imbalance, including molybdenum (Mo), as a potential link with AD occurrence.We conducted an extensive literature review of the last 60 years of research on AD and its relationship with Cu, sulfur (S), and Mo at out of range levels.Weanalyzed the interactions among metallic elements' metabolisms;Cu and Mo are biological antagonists, Mo is a sulfite oxidase and xanthine oxidase co-factor, and their low activities impair S metabolism and reduce uric acid, respectively. We found significant evidence in the literature of a new potential mechanism linking Cu imbalance to Mo and S abnormalities in AD etiology: under certain circumstances, the accumulation of Cu not bound to ceruloplasmin might affect the transport of Mo outside the blood vessels, causing a mild Mo deficiency that might lowerthe activity of Mo and S enzymes essential for neuronal activity. The current review provides an updated discussion of the plausible mechanisms combining Cu, S, and Mo alterations in AD.
Assuntos
Doença de Alzheimer , Molibdênio , Doença de Alzheimer/etiologia , Cobre/metabolismo , Dieta , Humanos , Molibdênio/metabolismo , EnxofreRESUMO
The retinotectal projection of rodents presents a precise retinotopic organization that develops, from diffuse connections, from the day of birth to post-natal day 10. Previous data had demonstrated that these projections undergo reorganization after retinal lesions, nerve crush and monocular enucleation. The axonal growth seems to be directly related to growth-associated protein-43 (GAP-43) expression, a protein predominantly located in growth cones, which is regulated throughout development. GAP-43 is presented both under non-phosphorylated and phosphorylated (pGAP-43) forms. The phosphorylated form, has been associated to axon growth via polymerization of F-actin, and synaptic enhancement through neurotransmitter release facilitation. Herein we investigated the spatio-temporal expression of GAP-43 in the rat superior colliculus during normal development and after monocular enucleation in different stages of development. Lister Hooded rats ranging from post-natal day 0 to 70 were used for ontogeny studies. Another group of animals were submitted to monocular enucleation at post-natal day 10 (PND10) or PND21. After different survival-times, the animals were sacrificed and the brains processed for either immunohistochemistry or western blotting analysis. Our data show that GAP-43 is expressed in retinotectal axons in early stages of development but remains present in adulthood. Moreover, monocular enucleation leads to an increase in pGAP-43 expression in the deafferented colliculus. Taken together these results suggest a role for pGAP-43 in retinotectal morphological plasticity observed both during normal development and after monocular enucleation.