Abstract
BackgroundImmune system dysregulation is well-recognized in autism and thought to be part of the etiology of this disorder. The endocannabinoid system is a key regulator of the immune system via the cannabinoid receptor type 2 (CB2R) which is highly expressed on macrophages and microglial cells. We have previously published significant differences in peripheral blood mononuclear cell CB2R gene expression in the autism population. The use of the Gc protein-derived Macrophage Activating Factor (GcMAF), an endogenous glycosylated vitamin D binding protein responsible for macrophage cell activation has demonstrated positive effects in the treatment of autistic children. In this current study, we investigated the in vitro effects of GcMAF treatment on the endocannabinoid system gene expression, as well as cellular activation in blood monocyte-derived macrophages (BMDMs) from autistic patients compared to age-matched healthy developing controls.MethodsTo achieve these goals, we used biomolecular, biochemical and immunocytochemical methods.ResultsGcMAF treatment was able to normalize the observed differences in dysregulated gene expression of the endocannabinoid system of the autism group. GcMAF also down-regulated the over-activation of BMDMs from autistic children.ConclusionsThis study presents the first observations of GcMAF effects on the transcriptionomics of the endocannabinoid system and expression of CB2R protein. These data point to a potential nexus between endocannabinoids, vitamin D and its transporter proteins, and the immune dysregulations observed with autism.
Highlights
Autism and autism spectrum disorders (ASDs) are complex heterogeneous neurodevelopmental conditions [1], arising from the interaction of genetic and environmental factors [2]
We recently demonstrated that a cannabinoid receptor type 2 (CB2R) signalling was significantly upregulated in peripheral blood mononuclear cells (PBMCs) extracted from autistic children, suggesting that endocannabinoid (EC) system dysregulation could be involved in ASDmediated immune impairments [19]
We observed that the mRNA levels of the FAAH enzyme gene were decreased; the NAPE-PLD/FAAH ratio was significantly increased; mRNA levels of CB2R gene were not changed (Figure 2)
Summary
Autism and autism spectrum disorders (ASDs) are complex heterogeneous neurodevelopmental conditions [1], arising from the interaction of genetic and environmental factors [2]. Vitamin D deficiency in pregnancy or early childhood appears to contribute significantly to risk [15]. The use of the Gc protein-derived Macrophage Activating Factor (GcMAF), an endogenous glycosylated vitamin D binding protein responsible for macrophage cell activation has demonstrated positive effects in the treatment of autistic children. In this current study, we investigated the in vitro effects of GcMAF treatment on the endocannabinoid system gene expression, as well as cellular activation in blood monocyte-derived macrophages (BMDMs) from autistic patients compared to age-matched healthy developing controls
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