当前位置： SCI文献检索 > LIFE SCIENCES期刊下所有文献 > The potent immunomodulatory compound VGX-1027 regulates inflammatory mediators in CD4+ T cells, which are concomitant with the prevention of neuroimmune dysregulation in BTBR T+ Itpr3tf/J mice.

The potent immunomodulatory compound VGX-1027 regulates inflammatory mediators in CD4+ T cells, which are concomitant with the prevention of neuroimmune dysregulation in BTBR T+ Itpr3tf/J mice.

Abstract：

:Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by symptoms that include social communication impairments, interaction deficits, and repetitive and stereotyped behaviors. Recent studies have suggested that imbalanced cytokine levels are associated with impaired behavioral outcomes in individuals with ASD. VGX-1027 is a potent immunomodulatory compound that has shown promise for the treatment of several neuroinflammatory disorders. Here, we studied the effects of VGX-1027 on BTBR T+ Itpr3tf/J (BTBR) mice, an animal model of autism. BTBR mice exhibit most of the core behavioral features of ASD, such as reduced sociability and increased repetitive behaviors. In this study, we investigated the effects of VGX-1027 on self-grooming, marble burying and sociability tests using BTBR mice. We further examined its effect on IL-1β, IL-6, IL-10, TNF-α, IFN-γ, and NF-κB p65 production in splenic CD4+ cells and on IL-1β, IL-6, IL-10, TNF-α, IFN-γ, COX-2, and iNOS (NOS2) protein and mRNA expression in brain tissues. The administration of VGX-1027 was found to attenuate self-grooming and marble burying behaviors, and enhance social interactions in BTBR mice. Additionally, VGX-1027 treatment resulted in a substantial decrease in IL-1β, IL-6, TNF-α, IFN-γ, and NF-κB p65 production, but increased IL-10 production in CD4+ T cells. Moreover, this agent was also found to significantly decrease IL-1β, IL-6, TNF-α, IFN-γ, COX-2, and NOS2 levels and increase IL-10 expression at the protein and mRNA level in brain tissues. Based on results using BTBR mice, our data provide the first evidence that VGX-1027 could potentially be used for the amelioration of autism-like symptoms.

journal_name

Life Sci

journal_title

Life sciences

authors

Ahmad SF,Nadeem A,Ansari MA,Bakheet SA,Alasmari F,Alasmari AF,Al-Kharashi LA,Al-Qahtani QH,Attia SM

doi

10.1016/j.lfs.2019.116930

subject

Has Abstract

pub_date

2019-11-15 00:00:00

pages

116930

eissn

0024-3205

issn

1879-0631

pii

S0024-3205(19)30857-4

journal_volume

237

pub_type

杂志文章

在线工具

The potent immunomodulatory compound VGX-1027 regulates inflammatory mediators in CD4+ T cells, which are concomitant with the prevention of neuroimmune dysregulation in BTBR T+ Itpr3tf/J mice.