Glatiramer promotes oligodendroglial cell maturation in a cuprizone-induced demyelination model

Siri, María Victoria Rosato; Badaracco, Maria; Pasquini, Juana M.

doi:10.1016/j.neuint.2013.04.008

Cited by 15 publications

(14 citation statements)

References 38 publications

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“…In contrast, the number of IBA1-positive microglia increased in the hippocampus of a rat model of cranial irradiation-induced brain injury [162] and GA-treated cuprizone mice showed an expansion of MAC-1 and CD68-positive M1 microglia numbers [170]. Moreover, in primary cultures, the number of MAC-1-positive microglia was increased following the GA treatment [170]. Furthermore, GA treatment induced a phagocytic phenotype in cultured rat microglia cells [171] and increased the bacterial phagocytosis of IFN-γ-stimulated primary microglia [172], but not the phagocytosis of autologous human peripheral blood-derived mononuclear cells [173].…”

Section: Microgliamentioning

confidence: 86%

“…In line with this, the migration of GA-exposed T-cells into the brains of EAE mice resulted in the increased expression of the anti-inflammatory microglial markers IL-10 and transforming growth factor-beta 2 (TGF-β2) [174], but the GA-treated co-cultures of microglia and activated T-lymphocytes showed a reduction of IL-10 [168]. Furthermore, cultured GA-treated microglia showed increased IL-10 and IL-4 secretion [170,171], again supporting a possible switch from M1 to M2 microglia following GA treatment. Another contributor to a diminished pro-inflammatory environment is the reduction in the levels of the IL-17 protein, a strong inducer of inflammation, in GA-treated EAE mice [164].…”

Section: Microgliamentioning

confidence: 91%

“…In addition, the morphological transformation of ramified resting microglia into a pro-inflammatory amoeboid morphology was attenuated in vitro by GA in human primary fetal and adult microglia activated by T-lymphocytes [168] and in EAE-mouse slice cultures [169]. In contrast, the number of IBA1-positive microglia increased in the hippocampus of a rat model of cranial irradiation-induced brain injury [162] and GA-treated cuprizone mice showed an expansion of MAC-1 and CD68-positive M1 microglia numbers [170]. Moreover, in primary cultures, the number of MAC-1-positive microglia was increased following the GA treatment [170].…”

Section: Microgliamentioning

confidence: 98%

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Molecular Effects of FDA-Approved Multiple Sclerosis Drugs on Glial Cells and Neurons of the Central Nervous System

Kleijn

Martens

2020

IJMS

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Multiple sclerosis (MS) is characterized by peripheral and central inflammatory features, as well as demyelination and neurodegeneration. The available Food and Drug Administration (FDA)-approved drugs for MS have been designed to suppress the peripheral immune system. In addition, however, the effects of these drugs may be partially attributed to their influence on glial cells and neurons of the central nervous system (CNS). We here describe the molecular effects of the traditional and more recent FDA-approved MS drugs Fingolimod, Dimethyl Fumarate, Glatiramer Acetate, Interferon-β, Teriflunomide, Laquinimod, Natalizumab, Alemtuzumab and Ocrelizumab on microglia, astrocytes, neurons and oligodendrocytes. Furthermore, we point to a possible common molecular effect of these drugs, namely a key role for NFκB signaling, causing a switch from pro-inflammatory microglia and astrocytes to anti-inflammatory phenotypes of these CNS cell types that recently emerged as central players in MS pathogenesis. This notion argues for the need to further explore the molecular mechanisms underlying MS drug action.

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Section: Microgliamentioning

confidence: 86%

Section: Microgliamentioning

confidence: 91%

Section: Microgliamentioning

confidence: 98%

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Molecular Effects of FDA-Approved Multiple Sclerosis Drugs on Glial Cells and Neurons of the Central Nervous System

Kleijn

Martens

2020

IJMS

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“…Along with the well‐described increase in the population of OLG precursors (Adamo et al, ; Rosato Siri et al, ), CPZ generates a deleterious effect on mature OLG (Bénardais et al, ; Matsushima and Morell, ). CPZ administration before weaning coincides with the ontogenetic myelination process and may dramatically affect the few mature OLG present at this moment and the ones concomitantly maturing, thus producing dysmyelination or a delay in ontogenetic myelination rather than demyelination.…”

Section: Discussionmentioning

confidence: 99%

“…Immunohistochemistry was performed as described by Rosato Siri et al (). Primary antibody specifications: anti‐MBP (Marker of myelin); Gift from Dr. A. Campagnoni, UCLA; Rabbit, Polyclonal; working dilution (wd) 1:500.…”

Section: Methodsmentioning

confidence: 99%

Gender influence on schizophrenia‐relevant abnormalities in a cuprizone demyelination model

Valeiras

Siri

Codagnone

et al. 2014

Glia

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The aim of this study was to determine whether early demyelination can impact behavior in young adulthood. For this purpose, albino Wistar rats of either sex were exposed to cuprizone (CPZ) in two different intoxication protocols: one group was intoxicated before weaning (CPZ-BW), from postnatal day 7 (P7) to P21, through maternal milk, whereas the other group was intoxicated after weaning (CPZ-AW), from P21 to P35. After treatment, rats were returned to a normal diet until P90 when behavioral studies were performed. Both treatments produced marked demyelination in the corpus callosum and retraction of cortical myelin fibers. The subsequent normal diet allowed for effective remyelination at P90. Interestingly, CPZ-AW correlated with significant behavioral and neurochemical changes in a gender-dependent manner. CPZ-AW treatment altered both the number of social activities and the latency to the first social interaction in males, while also highly compromising recognition-related activities. In addition, only P90 males treated AW showed a hyperdopaminergic striatum, confirmed by an increase in tyrosine hydroxylase expression and in dopamine levels. Our results suggest that the timing of demyelination significantly influences the development of altered behavior, particularly in adult males.

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Oligodendrogenesis and myelinogenesis during postnatal development effect of glatiramer acetate

From

Bar-Lev

Levin-Zaidman

et al. 2014

Glia

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Myelinogenesis in the mammal nervous system occurs predominantly postnatally. Glatiramer acetate (GA), a drug for the treatment for multiple sclerosis (MS), has been shown to induce immunomodulation and neuroprotection in the inflamed CNS in MS and in experimental autoimmune encephalomyelitis (EAE). Here we investigated whether GA can affect myelinogenesis and oligodendrogenesis in the developing nervous system under nonpathological conditions. Towards this end we studied myelination in mice injected daily by GA, at postnatal Days 7-21. Immunohistological and ultrastructural analyses revealed significant elevation in the number of myelinated axons as well as in the thickness of the myelin encircling them and their resulting g-ratios, in spinal cords of GA-injected mice compared with their PBS-injected littermates, at postnatal Day 14. Elevation in myelinated axons was detected also in the peripheral ventral roots of the motor nerves. GA induced also an increase in axonal diameter, implying an effect on the overall development of the nervous system. A prominent elevation in the amount of progenitor oligodendrocytes and their BrdU incorporation, as well as in mature oligodendrocytes indicated that the effect of GA is linked to increased proliferation and differentiation along the oligodendroglial maturation cascade. In addition, elevation in insulin-like growth factor (IGF-1) and brain-derived neurotrophic factor (BDNF) was found in the white matter of the GA-injected mice. Furthermore, a functional advantage in rotating rod test was exhibited by GA-injected mice over their littermates at postnatal Day 21. These cumulative findings corroborate the beneficial effect of GA on oligodendrogenesis and myelination.

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Glatiramer promotes oligodendroglial cell maturation in a cuprizone-induced demyelination model

Cited by 15 publications

References 38 publications

Molecular Effects of FDA-Approved Multiple Sclerosis Drugs on Glial Cells and Neurons of the Central Nervous System

Molecular Effects of FDA-Approved Multiple Sclerosis Drugs on Glial Cells and Neurons of the Central Nervous System

Gender influence on schizophrenia‐relevant abnormalities in a cuprizone demyelination model

Oligodendrogenesis and myelinogenesis during postnatal development effect of glatiramer acetate

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