Treatment In vitro of Retinal Cells with IL-4 Increases the Survival of Retinal Ganglion Cells: The Involvement of BDNF

Araujo-Martins, Leandro de; Oliveira, Raphael Monteiro de; Santos, Gabriela Velozo Gomes dos; Santos, R.C.C.; Santos, Aline Araújo dos; Araújo, Elizabeth Giestal de

doi:10.1007/s11064-012-0904-0

Cited by 12 publications

(9 citation statements)

References 47 publications

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“…We already know that M3 mAChR and IL-4 levels increase during retinal development (Araújo-Martins et al 2013;Braga et al 2013) and in the present work we show that IL-4 increases the levels of this muscarinic receptors mimicking what occurs during the normal development. Taken together, the results presented in this study demonstrate the influence of IL-4 in differentiation process of cholinergic cells from neonatal rat retina and suggests an important role for this cytokine in the development of cholinergic phenotype in the retinal tissue.…”

Section: Cell Mol Neurobiolsupporting

confidence: 82%

“…5a). However, our group had already shown that treatment with IL-4 for 15 min induces an increase in the levels of phosphor-CREB (Araújo- Martins et al 2013). Treatment of human astrocytoma with carbamylcholine, a non-hydrolysable analog of Ach, induces NFjB activation and this effect was mediated by M3 mAChRs activation, calcium mobilization, and activation of PKC (Guizzetti et al 2003).…”

Section: Discussionmentioning

confidence: 99%

“…Previously, our group demonstrated that treatment with IL-4, for 15 min, induced an increase of 100 % in the levels of phosphor-CREB in the retinal cell cultures (Araújo- Martins et al 2013). Based on this result, we investigated the levels of phosphor-CREB after IL-4 treatment for 48 h to analyze a possible involvement of this transcription factor in the increase of M3 mAChRs levels in our experimental model.…”

Section: The Transcription Factor Involved On Il-4 Effectmentioning

confidence: 91%

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IL-4 Induces Cholinergic Differentiation of Retinal Cells In Vitro

et al. 2015

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Interleukin-4 (IL-4) is a pleiotropic cytokine that regulates several phenomena, among them survival and differentiation of neuronal and glial cells. The aim of this work was to investigate the effect of IL-4 on the cholinergic differentiation of neonatal rat retinal cells in vitro, evaluating its effect on the levels of cholinergic markers (CHT1-high-affinity choline transporter; VAChT-vesicular acetylcholine transporter, ChAT-choline acetyltransferase, AChE-acetylcholinesterase), muscarinic receptors, and on the signaling pathways involved. Lister Hooded rat pups were used in postnatal days 0-2 (P0-P2). Our results show that IL-4 treatment (50 U/mL) for 48 h increases the levels of the cholinergic transporters VAChT and CHT1, the acetylcholinesterase activity, and the number of ChAT-positive cells. It also induces changes in muscarinic receptor levels, leading to a small decrease in M1 levels and a significant increase in M3 and M5 levels after 48 h of treatment. We also showed that IL-4 effect on M3 receptors is dependent on type I IL-4 receptor and on an increase in NFκB phosphorylation. These results indicate that IL-4 stimulates cholinergic differentiation of retinal cells.

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Section: Cell Mol Neurobiolsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

Section: The Transcription Factor Involved On Il-4 Effectmentioning

confidence: 91%

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IL-4 Induces Cholinergic Differentiation of Retinal Cells In Vitro

et al. 2015

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“…It has been reported that the altertion of BDNF and NGF appears to be mediated by skewing the Th1/Th2 balance toward Th2 type by inhibition of IFN‐γ and enhanced IL‐4 production in the CNS of EAE (Villoslada et al, ; Arredondo et al, ; Makar et al, ). IL‐4 treatment increases BDNF expression in retinal ganglion cells of newborn rat culture and there is an increased production of mRNA for BDNF when astrocytes are incubated with IL‐4, which suggest that BDNF is the neurotrophin involved in IL‐4 effect (Kerschensteiner et al, ; Derecki et al, ; de Araujo‐Martins et al, ). IL‐4 has also been shown to increase the synthesis of NGF by astrocytes, lymphocytes, and C6 glial cells (Brodie and Goldreich, ; Brodie et al, ; Arredondo et al, ).…”

Section: Discussionmentioning

confidence: 99%

Ginsenoside Rd ameliorates experimental autoimmune encephalomyelitis in C57BL/6 mice

Zhu

Liu

Yang

et al. 2014

J of Neuroscience Research

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Multiple sclerosis (MS) is a common disabling autoimmune disease without an effective treatment in young adults. Ginsenoside Rd, extracted from Panax notoginseng, has multiple pharmacological effects and potential therapeutic applications in diseases of the central nervous system. In this study, we explore the efficacy of ginsenoside Rd in experimental autoimmune encephalomyelitis (EAE), an established model of MS. EAE was induced by myelin oligodendrocyte glycoprotein 35-55-amino-acid peptide. Ginsenoside Rd (10-80 mg/kg/day) or vehicle was intraperitoneally administered on the disease onset day, and the therapy persisted throughout the experiments. The dose of 40 mg/kg/day of ginsenoside Rd was selected as optimal. Ginsenoside Rd effectively ameliorated the clinical severity in EAE mice, reduced the permeability of the blood-brain barrier, regulated the secretion of interferon-gamma and interleukin-4, promoted the Th2 shift in vivo (cerebral cortex) and in vitro (splenocytes culture supernatants), and prevented the reduction in expression of brain-derived neurotrophic factor and nerve growth factor in both cerebral cortex and lumbar spinal cord of EAE mice. This study establishes the potency of ginsenoside Rd in inhibiting the clinical course of EAE. These findings suggest that ginsenoside Rd could be a promising agent for amelioration of neuroimmune dysfunction diseases such as MS.

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“…Signal transduction through IL-4Rs involves 3 major pathways: JAK-STAT6, Raf-MEK-ERK and PI3K-Akt [1,3]. Several studies have pointed out the role of IL-4 in different processes of brain development such as neuronal survival [7,8], proliferation [6], differentiation [6,9], and synaptic plasticity [10]. However, the impact of an anti-inflammatory cytokine in the organization of central connections has not yet been reported.…”

Section: Introductionmentioning

confidence: 99%

Interleukin 4 Leads to Sustained Phosphorylation of the STAT6 and ERK Pathways in the Retina and Disrupts Subcortical Visual Circuitry in Rodents

Goulart¹,

Menezes²,

Espírito-Santo³

et al. 2018

Neuroimmunomodulation

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Objective: Interleukin 4 (IL-4) is an anti-inflammatory cytokine related to different aspects of central nervous system development such as survival, proliferation, and differentiation, among others. Our goals were to investigate the effect of intravitreous treatment with IL-4 on the activation of downstream signaling pathways in the retina and the distribution of retinal axons within the superior colliculus (SC). Material and Methods: Lister hooded rats were submitted to an intravitreous injection of either IL-4 (5 U/µL) or PBS (vehicle) at postnatal day 10 (PND10). At PND11 or PND14, retinas were processed for Western blot or immunohistochemistry. At PND13, a group of animals received an intraocular injection of an anterograde tracer in the left (untreated) eye in order to label the uncrossed retinotectal axons. Results: Our data revealed that intravitreous treatment with IL-4 at PND10 leads to a decrease in GFAP content and a sustained increase in the phosphorylation of STAT6 and ERK levels in the retina. IL-4 also increases retinal axonal arbors within the SC, compared to control groups. Conclusions: These data suggest that a single in vivo treatment with IL-4 during the early stages of development modulates signaling pathways in the retina, resulting in altered binocular subcortical visual connectivity.

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Treatment In vitro of Retinal Cells with IL-4 Increases the Survival of Retinal Ganglion Cells: The Involvement of BDNF

Cited by 12 publications

References 47 publications

IL-4 Induces Cholinergic Differentiation of Retinal Cells In Vitro

IL-4 Induces Cholinergic Differentiation of Retinal Cells In Vitro

Ginsenoside Rd ameliorates experimental autoimmune encephalomyelitis in C57BL/6 mice

Interleukin 4 Leads to Sustained Phosphorylation of the STAT6 and ERK Pathways in the Retina and Disrupts Subcortical Visual Circuitry in Rodents

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