Abstract:
:Increased expression of S100B and its specific receptor for advanced glycation end products (RAGE) has been described in patients with multiple sclerosis (MS), being associated with an active demyelinating process. We previously showed that a direct neutralization of S100B reduces lysophosphatidylcholine (LPC)-induced demyelination and inflammation using an ex vivo demyelinating model. However, whether S100B actions occur through RAGE and how oligodendrogenesis and remyelination are affected are not clarified. To evaluate the role of the S100B-RAGE axis in the course of a demyelinating insult, organotypic cerebellar slice cultures (OCSC) were demyelinated with LPC in the presence or absence of RAGE antagonist FPS-ZM1. Then, we explored the effects of the S100B-RAGE axis inhibition on glia reactivity and inflammation, myelination and neuronal integrity, and on oligodendrogenesis and remyelination. In the present study, we confirmed that LPC-induced demyelination increased S100B and RAGE expression, while RAGE antagonist FPS-ZM1 markedly reduced their content and altered RAGE cellular localization. Furthermore, FPS-ZM1 prevented LPC-induced microgliosis and astrogliosis, as well as NF-κB activation and pro-inflammatory cytokine gene expression. In addition, RAGE antagonist reduced LPC-induced demyelination having a beneficial effect on axonal and synaptic protein preservation. We have also observed that RAGE engagement is needed for LPC-induced oligodendrocyte (OL) maturation arrest and loss of mature myelinating OL, with these phenomena being prevented by FPS-ZM1. Our data suggest that increased levels of mature OL in the presence of FPS-ZM1 are related to increased expression of microRNAs (miRs) associated with OL differentiation and remyelination, such as miR-23a, miR-219a, and miR-338, which are defective upon LPC incubation. Finally, our electron microscopy data show that inhibition of the S100B-RAGE axis prevents axonal damage and myelin loss, in parallel with enhanced functional remyelination, as observed by the presence of thinner myelin sheaths when compared with Control. Overall, our data implicate the S100B-RAGE axis in the extent of myelin and neuronal damage, as well as in the inflammatory response that follows a demyelinating insult. Thus, prevention of RAGE engagement may represent a novel strategy for promoting not only inflammatory reduction but also neuronal and myelin preservation and/or remyelination, improving recovery in a demyelinating condition as MS.
journal_name
Front Cell Neuroscijournal_title
Frontiers in cellular neuroscienceauthors
Santos G,Barateiro A,Brites D,Fernandes Adoi
10.3389/fncel.2020.00279subject
Has Abstractpub_date
2020-09-04 00:00:00pages
279issn
1662-5102journal_volume
14pub_type
杂志文章abstract::Neurosteroids are cholesterol-based hormones that can be produced in the brain, independent of secretion from peripheral endocrine glands, such as the gonads and adrenals. A focus in our laboratory for over 25 years has been how production of the pregnane neurosteroid, allopregnanolone, is regulated and the novel (i.e...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fncel.2014.00106
更新日期:2014-04-09 00:00:00
abstract::Heterotrimeric G-proteins mediate a variety of cellular functions, including signal transduction in sensory neurons of the olfactory system. Whereas the Gα subunits in these neurons are well characterized, the gene transcript expression profile of Gβγ subunits is largely missing. Here we report our comprehensive expre...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2013.00084
更新日期:2013-06-04 00:00:00
abstract::Circadian behavioral rhythms offer an excellent model to study intricate interactions between the molecular and neuronal mechanisms of behavior. In mammals, pacemaker neurons in the suprachiasmatic nucleus (SCN) generate rhythms cell-autonomously, which are synchronized by the network interactions within the circadian...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2017.00317
更新日期:2017-10-12 00:00:00
abstract::The opioid peptide receptors consist of three major subclasses, namely, μ, δ, and κ (MOR, DOR, and KOR, respectively). They are involved in the regulation of striatal dopamine functions, and increased opioid transmissions are thought to play a compensatory role in altered functions of the basal ganglia in Parkinson's ...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2013.00074
更新日期:2013-05-17 00:00:00
abstract::Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease manifested by progressive muscle atrophy and paralysis due to the loss of upper and lower motoneurons (MN). Spasticity appears in ALS patients leading to further disabling consequences. Loss of the inhibitory tone induced by downregulation of the potas...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2014.00007
更新日期:2014-01-24 00:00:00
abstract::[This corrects the article DOI: 10.3389/fncel.2017.00013.]. ...
journal_title:Frontiers in cellular neuroscience
pub_type: 已发布勘误
doi:10.3389/fncel.2019.00303
更新日期:2019-07-09 00:00:00
abstract::Microglia, the immune competent cells of the central nervous system (CNS), normally exist in a resting state characterized by a ramified morphology with many processes, and become activated to amoeboid morphology in response to brain injury, infection, and a variety of neuroinflammatory stimuli. Many studies focused o...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2018.00309
更新日期:2018-09-11 00:00:00
abstract::Many neurodegenerative disorders are linked to irreversible protein aggregation, a process that usually comes along with toxicity and serious cellular damage. However, it is emerging that protein aggregation can also serve for physiological purposes, as impressively shown for prions. While the aggregation of this prot...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fncel.2015.00045
更新日期:2015-02-18 00:00:00
abstract::Neuron-glia interactions contribute to tissue homeostasis and functional plasticity in the mammalian brain, but it remains unclear how this is achieved. The potential of central auditory brain tissue for stimulation-dependent cellular remodeling was studied in hearing-experienced and neonatally deafened rats. At adult...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2018.00043
更新日期:2018-02-22 00:00:00
abstract::A fundamental interest in circuit analysis is to parse out the synaptic inputs underlying a behavioral experience. Toward this aim, we have devised an unbiased strategy that specifically labels the afferent inputs that are activated by a defined stimulus in an activity-dependent manner. We validated this strategy in f...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2020.00114
更新日期:2020-05-12 00:00:00
abstract::[This corrects the article on p. 396 in vol. 8, PMID: 25505873.]. ...
journal_title:Frontiers in cellular neuroscience
pub_type: 已发布勘误
doi:10.3389/fncel.2015.00160
更新日期:2015-04-23 00:00:00
abstract::Sections from the middle frontal gyrus (Brodmann area 46) of autopsy-confirmed Alzheimer's disease (AD) patients and non-demented subjects were examined for the prevalence of hallmark AD pathology, including amyloid-β (Aβ) plaques, phosphorylated tau (pTau) tangles, neuroinflammation and synaptic loss (n = 7 subjects/...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2019.00538
更新日期:2019-12-05 00:00:00
abstract::Adeno-associated virus (AAV) is the preferred vector for gene therapy of hereditary deafness, and different viral serotypes, promoters and transduction pathways can influence the targeting of AAV to different types of cells and the expression levels of numerous exogenous genes. To determine the transduction and expres...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2019.00008
更新日期:2019-01-24 00:00:00
abstract::Natural products have attracted interest in the search for new and effective analgesics and coadjuvant approaches to several types of pain. It is in fact well known that many of their active ingredients, such as anthocyanins (ACNs) and polyphenols, can exert potent anti-inflammatory actions. Nevertheless, their potent...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2018.00378
更新日期:2018-11-05 00:00:00
abstract::The use of human pluripotent stem cells (PSCs) for cell therapy faces a number of challenges that are progressively answered by results from clinical trials and experimental research. Among these is the control of differentiation before transplantation and the prediction of cell fate after administration into the huma...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2012.00002
更新日期:2012-01-27 00:00:00
abstract::IN ADULT MAMMALS, UNDER PHYSIOLOGICAL CONDITIONS, NEUROGENESIS, THE PROCESS OF GENERATING NEW FUNCTIONAL NEURONS FROM PRECURSOR CELLS, OCCURS MAINLY IN TWO BRAIN AREAS: the subgranular zone in the dentate gyrus of the hippocampus, and the subventricular zone (SVZ) lining the walls of the brain lateral ventricles. Taki...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2012.00034
更新日期:2012-08-09 00:00:00
abstract::Optogenetic and pharmacogenetic techniques have been effective to analyze the role of neuronal activity in controlling oligodendroglia lineage cells in behaving juvenile and adult mice. This kind of studies is also of high interest during early postnatal (PN) development since important changes in oligodendroglia dyna...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2018.00477
更新日期:2018-12-06 00:00:00
abstract:OBJECTIVE:Neuroinflammation in utero may result in life-long neurological disabilities. The molecular mechanisms whereby microglia contribute to this response remain incompletely understood. METHODS:Lipopolysaccharide (LPS) or saline were administered intravenously to non-anesthetized chronically instrumented near-ter...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2015.00294
更新日期:2015-08-04 00:00:00
abstract::Disturbances in mitochondrial biogenesis and bioenergetics, combined with neuroinflammation, play cardinal roles in the cognitive impairment during aging that is further exacerbated by transient cerebral ischemia. Both near-infrared (NIR) photobiomodulation (PBM) and Coenzyme Q10 (CoQ10) administration are known to st...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2019.00074
更新日期:2019-03-19 00:00:00
abstract::In this review, we discuss molecular and cellular mechanisms important for the function of neuronal progenitors during development, revealed by their perturbation in different cortical malformations. We focus on a class of neuronal progenitors, radial glial cells (RGCs), which are renowned for their unique morphologic...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fncel.2015.00030
更新日期:2015-02-12 00:00:00
abstract::One century after its first description, pathology of Alzheimer's disease (AD) is still poorly understood. Amyloid-related dendritic atrophy and membrane alterations of susceptible brain neurons in AD, and in animal models of AD are widely recognized. However, little effort has been made to study the potential effects...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2016.00152
更新日期:2016-06-16 00:00:00
abstract::There is evidence for both neurotoxic and neuroprotective roles of nitric oxide (NO) in the brain and changes in the expression of the neuronal isoform of NO synthase (nNOS) gene occur during aging. The current studies have investigated potential support for either a neurotoxic or neuroprotective role of NO derived fr...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2015.00105
更新日期:2015-03-27 00:00:00
abstract::Nitric oxide (NO) is a pleiotropic janus-faced molecule synthesized by nitric oxide synthases (NOS) which plays a critical role in a number of physiological and pathological processes in humans. The physiological roles of NO depend on its local concentrations, as well as its availability and the nature of downstream t...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fncel.2015.00322
更新日期:2015-08-17 00:00:00
abstract::The microtubule-associated axonal specification collapsin response mediator protein 2 (CRMP2) is a novel target for neuroprotection. A CRMP2 peptide (TAT-CBD3) conjugated to the HIV transactivator of transcription (TAT) protein's cationic cell penetrating peptide (CPP) motif protected neurons in the face of toxic leve...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2014.00471
更新日期:2015-01-26 00:00:00
abstract::Topographical and biochemical characteristics of the substrate are critical for neuronal differentiation including axonal outgrowth and regeneration of neural circuits in vivo. Contact stimuli and signaling molecules allow neurons to develop and stabilize synaptic contacts. Here we present the development, characteriz...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2012.00010
更新日期:2012-03-14 00:00:00
abstract::Huntington's disease (HD) is an autosomal-dominant inherited neurodegenerative disorder characterized by motor, psychiatric and cognitive symptoms. HD is caused by an expansion of CAG repeats in the huntingtin (HTT) gene in various areas of the brain including striatum. There are few suitable animal models to study th...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2018.00157
更新日期:2018-06-12 00:00:00
abstract::Gastrointestinal (GI) pain is a common clinical problem, for which effective therapy is quite limited. Sensations from the GI tract, including pain, are mediated largely by neurons in the dorsal root ganglia (DRG), and to a smaller extent by vagal afferents emerging from neurons in the nodose/jugular ganglia. Neurons ...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fncel.2015.00412
更新日期:2015-10-13 00:00:00
abstract::Biologically relevant large-scale computational models currently represent one of the main methods in neuroscience for studying information processing primitives of brain areas. However, biologically realistic neuron models tend to be computationally heavy and thus prevent these models from being part of brain-area mo...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章
doi:10.3389/fncel.2020.00161
更新日期:2020-07-14 00:00:00
abstract::[This corrects the article DOI: 10.3389/fncel.2019.00150.]. ...
journal_title:Frontiers in cellular neuroscience
pub_type: 已发布勘误
doi:10.3389/fncel.2019.00388
更新日期:2019-08-22 00:00:00
abstract::When retrieval occurs concomitantly with novelty detection, mismatch perception or reactivation of conflicting information, consolidated memories can enter into a labile state, and to persist, must be restabilized through a protein synthesis-dependent reconsolidation process during which their strength and content can...
journal_title:Frontiers in cellular neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fncel.2019.00383
更新日期:2019-08-22 00:00:00