The anti-inflammatory peptide stearyl-norleucine-VIP delays disease onset and extends survival in a rat model of inherited amyotrophic lateral sclerosis

Goursaud, Stéphanie; Schäfer, Sabrina; Dumont, Amélie; Vergouts, Maxime; Gallo, Alessandro; Desmet, Nathalie; Deumens, Ronald; Hermans, Emmanuel

doi:10.1016/j.expneurol.2014.09.022

Cited by 12 publications

(9 citation statements)

References 56 publications

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“…Moreover, all neuronal factors studied in the present investigations in NRG-1-positive nerves are known as substances acting on the immune system. Namely, SP through receptors on lymphocytes and macrophages enhances the secretion of pro-inflammatory factors [ 67 ], VIP keeps the balance between pro- and anti-inflammatory cytokines [ 68 , 69 ], and GAL is an anti-inflammatory substance which increases the levels of IFN-γ and IL-12/23 [ 70 ]. Even CART, which has roles in the modulation of the immune system, still remains not fully elucidated and plays important functions in modulating post-stroke immune processes [ 71 ].…”

Section: Discussionmentioning

confidence: 99%

The Influence of Bisphenol A (BPA) on Neuregulin 1-Like Immunoreactive Nerve Fibers in the Wall of Porcine Uterus

Rytel

2018

IJMS

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Bisphenol A (BPA), a substance commonly used in the manufacture of plastics, shows multidirectional negative effects on humans and animals. Due to similarities to estrogens, BPA initially leads to disorders in the reproductive system. On the other hand, it is known that neuregulin 1 (NRG-1) is an active substance which enhances the survivability of cells, inhibits apoptosis, and protects tissues against damaging factors. Because the influence of BPA on the nervous system has also been described, the aim of the present study was to investigate for the first time the influence of various doses of BPA on neuregulin 1-like immunoreactive (NRG-1-LI) nerves located in the porcine uterus using the routine single- and double-immunofluorescence technique. The obtained results have shown that BPA increases the number and affects the neurochemical characterization of NRG-1-LI in the uterus, and changes are visible even under the impact of small doses of this toxin. The character of observed changes depended on the dose of BPA and the part of the uterus studied. These observations suggest that NRG-1 in nerves supplying the uterus may play roles in adaptive and protective mechanisms under the impact of BPA.

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Section: Discussionmentioning

confidence: 99%

The Influence of Bisphenol A (BPA) on Neuregulin 1-Like Immunoreactive Nerve Fibers in the Wall of Porcine Uterus

Rytel

2018

IJMS

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“…Vasoactive intestinal peptide (VIP) exerts its immune modulatory actions by regulating IL-10 as well as neurotrophic factors in an mSOD1 model of ALS [45]. Similarly, Ayers et al [46] showed that IL-10 expression in the spinal axis prolonged the survival of SOD1-G93A mice.…”

Section: Discussionmentioning

confidence: 99%

Astroglia acquires a toxic neuroinflammatory role in response to the cerebrospinal fluid from amyotrophic lateral sclerosis patients

Mishra

Dhull

Nalini

et al. 2016

J Neuroinflammation

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BackgroundNon-cell autonomous toxicity is one of the potential mechanisms implicated in the etiopathogenesis of amyotrophic lateral sclerosis (ALS). However, the exact role of glial cells in ALS pathology is yet to be fully understood. In a cellular model recapitulating the pathology of sporadic ALS, we have studied the inflammatory response of astroglia following exposure to the cerebrospinal fluid from ALS patients (ALS-CSF).MethodsVarious inflammatory markers including pro-inflammatory and anti-inflammatory cytokines, COX-2, PGE-2, trophic factors, glutamate, nitric oxide (NO), and reactive oxygen species (ROS) were analyzed in the rat astroglial cultures exposed to ALS-CSF and compared with the disease control or normal controls. We used immunofluorescence, ELISA, and immunoblotting techniques to investigate the protein expression and real-time PCR to study the messenger RNA (mRNA) expression. Glutamate, NO, and ROS were estimated using appropriate biochemical assays. Further, the effect of conditioned medium from the astroglial cultures exposed to ALS-CSF on NSC-34 motor neuronal cell line was detected using the MTT assay. Statistical analysis was carried out using one-way ANOVA followed by Tukey’s post hoc test, or Student’s t test, as applicable.ResultsHere, we report that the ALS-CSF enhanced the production and release of inflammatory cytokines IL-6 and TNF-α, as well as COX-2 and PGE-2. Concomitantly, anti-inflammatory cytokine IL-10 and the beneficial trophic factors, namely VEGF and GDNF, were down-regulated. We also found impaired regulation of glutamate, NO, and ROS in the astroglial cultures treated with ALS-CSF. The conditioned medium from the ALS-CSF exposed astroglial cultures induced degeneration in NSC-34 cells.ConclusionsOur study demonstrates that the astroglial cells contribute to the neuroinflammation-mediated neurodegeneration in the in vitro model of sporadic ALS.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-016-0698-0) contains supplementary material, which is available to authorized users.

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“…Glial fibrillary acidic protein (GFAP) and ionized calcium‐binding adapter molecule 1 (Iba 1) were stained using 20‐µm‐thick transversal cryosections of L4/L5 lumbar spinal cord as described previously (Goursaud et al ., ). Antibodies were rabbit anti‐Iba 1 (1:1000; Wako, Osaka, Japan), goat anti‐rabbit IgG (H + L) Alexa Fluor®488 (Invitrogen, 1:500) and the monoclonal mouse anti‐GFAP‐Cy3™ (Sigma‐Aldrich, 1:500) diluted in a working solution containing 1% NGS and 1% Triton X‐100 in TBS pH 7.4.…”

Section: Methodsmentioning

confidence: 97%

Inhibition of the regulator of G protein signalling RGS4 in the spinal cord decreases neuropathic hyperalgesia and restores cannabinoid CB₁ receptor signalling

Bosier

Brolet

Muccioli

et al. 2015

British J Pharmacology

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BACKGROUND AND PURPOSERegulators of G protein signalling (RGS) are major determinants of metabotropic receptor activity, reducing the lifespan of the GTP-bound state of G proteins. Because the reduced potency of analgesic agents in neuropathic pain may reflect alterations in RGS, we assessed the effects of CCG 63802, a specific RGS4 inhibitor, on pain hypersensitivity and signalling through cannabinoid receptors, in a model of neuropathic pain. EXPERIMENTAL APPROACHThe partial sciatic nerve ligation (PSNL) model in male Sprague Dawley rats was used to measure paw withdrawal thresholds to mechanical (von Frey hairs) or thermal (Hargreaves method) stimuli, during and after intrathecal injection of CCG 63802. HEK293 cells expressing CB 1 receptors and conditional expression of RGS4 were used to correlate cAMP production and ERK phosphorylation with receptor activation and RGS4 action. KEY RESULTSTreatment of PSNL rats with CCG 63802, twice daily for 7 days after nerve injury, attenuated thermal hyperalgesia during treatment. Spinal levels of anandamide were higher in PSNL animals, irrespective of the treatment. Although expression of CB 1 receptors was unaffected, HU210-induced CB 1 receptor signalling was inhibited in PSNL rats and restored after intrathecal CCG 63802. In transfected HEK cells expressing CB 1 receptors and RGS4, inhibition of cAMP production, a downstream effect of CB 1 receptor signalling, was blunted after RGS4 overexpression. RGS4 expression also attenuated the CB 1 receptor-controlled activation of ERK1/2. CONCLUSIONS AND IMPLICATIONSInhibition of spinal RGS4 restored endogenous analgesic signalling pathways and mitigated neuropathic pain. Signalling through CB 1 receptors may be involved in this beneficial effect

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The anti-inflammatory peptide stearyl-norleucine-VIP delays disease onset and extends survival in a rat model of inherited amyotrophic lateral sclerosis

Cited by 12 publications

References 56 publications

The Influence of Bisphenol A (BPA) on Neuregulin 1-Like Immunoreactive Nerve Fibers in the Wall of Porcine Uterus

The Influence of Bisphenol A (BPA) on Neuregulin 1-Like Immunoreactive Nerve Fibers in the Wall of Porcine Uterus

Astroglia acquires a toxic neuroinflammatory role in response to the cerebrospinal fluid from amyotrophic lateral sclerosis patients

Inhibition of the regulator of G protein signalling RGS4 in the spinal cord decreases neuropathic hyperalgesia and restores cannabinoid CB₁ receptor signalling

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The anti-inflammatory peptide stearyl-norleucine-VIP delays disease onset and extends survival in a rat model of inherited amyotrophic lateral sclerosis

Cited by 12 publications

References 56 publications

The Influence of Bisphenol A (BPA) on Neuregulin 1-Like Immunoreactive Nerve Fibers in the Wall of Porcine Uterus

The Influence of Bisphenol A (BPA) on Neuregulin 1-Like Immunoreactive Nerve Fibers in the Wall of Porcine Uterus

Astroglia acquires a toxic neuroinflammatory role in response to the cerebrospinal fluid from amyotrophic lateral sclerosis patients

Inhibition of the regulator of G protein signalling RGS4 in the spinal cord decreases neuropathic hyperalgesia and restores cannabinoid CB1 receptor signalling

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Inhibition of the regulator of G protein signalling RGS4 in the spinal cord decreases neuropathic hyperalgesia and restores cannabinoid CB₁ receptor signalling