Cannabinoid Receptor Type 2, but not Type 1, is Up-Regulated in Peripheral Blood Mononuclear Cells of Children Affected by Autistic Disorders

Abstract

Autistic disorders (ADs) are heterogeneous neurodevelopmental disorders arised by the interaction of genes and environmental factors. Dysfunctions in social interaction and communication skills, repetitive and stereotypic verbal and non-verbal behaviours are common features of ADs. There are no defined mechanisms of pathogenesis, rendering curative therapy very difficult. Indeed, the treatments for autism presently available can be divided into behavioural, nutritional and medical approaches, although no defined standard approach exists. Autistic children display immune system dysregulation and show an altered immune response of peripheral blood mononuclear cells (PBMCs). In this study, we investigated the involvement of cannabinoid system in PBMCs from autistic children compared to age-matched normal healthy developing controls (age ranging 3–9 years; mean age: 6.06 ± 1.52 vs. 6.14 ± 1.39 in autistic children and healthy subjects, respectively). The mRNA level for cannabinoid receptor type 2 (CB2) was significantly increased in AD-PBMCs as compared to healthy subjects (mean ± SE of arbitrary units: 0.34 ± 0.03 vs. 0.23 ± 0.02 in autistic children and healthy subjects, respectively), whereas CB1 and fatty acid amide hydrolase mRNA levels were unchanged. mRNA levels of N-acylphosphatidylethanolamine-hydrolyzing phospholipase D gene were slightly decreased. Protein levels of CB-2 were also significantly increased in autistic children (mean ± SE of arbitrary units: 33.5 ± 1.32 vs. 6.70 ± 1.25 in autistic children and healthy subjects, respectively). Our data indicate CB2 receptor as potential therapeutic target for the pharmacological management of the autism care.

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Acknowledgments

First and foremost, we thank the many autism families who volunteered as participants in this research study. The authors gratefully thank Mr. Enzo Abate, Ms. Giovanna Gallone and the no-profit organizations “La Forza del Silenzio” and “Cancellautismo”—Italy for their useful assistance. We thank the Autism Research Institute, USA (ARI grant “Research that makes a difference” 2010) for financial support of this study. The authors would like to thank Dr. Sarah Costantino, Second University of Naples, for her useful assistance in image analysis.

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Correspondence to Dario Siniscalco.

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Siniscalco, D., Sapone, A., Giordano, C. et al. Cannabinoid Receptor Type 2, but not Type 1, is Up-Regulated in Peripheral Blood Mononuclear Cells of Children Affected by Autistic Disorders. J Autism Dev Disord 43, 2686–2695 (2013). https://doi.org/10.1007/s10803-013-1824-9

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Keywords

  • Autistic disorders
  • Cannabinoid system
  • Gene expression
  • PBMCs