Common targetable inflammatory pathways in brain transcriptome of autism spectrum disorders and Tourette syndrome

Sarah Alshammery; Shrujna Patel; Hannah F Jones; Velda X Han; Brian S Gloss; Wendy A Gold; Russell C Dale

doi:10.3389/fnins.2022.999346

Common targetable inflammatory pathways in brain transcriptome of autism spectrum disorders and Tourette syndrome

Front Neurosci. 2022 Dec 15:16:999346. doi: 10.3389/fnins.2022.999346. eCollection 2022.

Authors

Sarah Alshammery^{1

2}, Shrujna Patel^{1

2}, Hannah F Jones^{1

2

3}, Velda X Han^{1

4}, Brian S Gloss⁵, Wendy A Gold^{1

2}, Russell C Dale^{1

2

6}

Affiliations

¹ Kids Neuroscience Centre, The Children's Hospital at Westmead, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.
² The Children's Hospital at Westmead Clinical School, Faculty of Medicine and Health, University of Sydney, Sydney, NSW, Australia.
³ Department of Neuroservices, Starship Children's Hospital, Auckland, New Zealand.
⁴ Khoo Teck Puat-National University Children's Medical Institute, National University Health System, Singapore, Singapore.
⁵ Westmead Research Hub, Westmead Institute for Medical Research, Westmead, NSW, Australia.
⁶ The Brain and Mind Centre, The University of Sydney, Sydney, NSW, Australia.

Abstract

Neurodevelopmental disorders (NDDs), including autism-spectrum disorders (ASD) and Tourette syndrome (TS) are common brain conditions which often co-exist, and have no approved treatments targeting disease mechanisms. Accumulating literature implicates the immune system in NDDs, and transcriptomics of post-mortem brain tissue has revealed an inflammatory signal. We interrogated two RNA-sequencing datasets of ASD and TS and identified differentially expressed genes, to explore commonly enriched pathways through GO, KEGG, and Reactome. The DEGs [False Discovery Rate (FDR) <0.05] in the ASD dataset (n = 248) and the TS dataset (n = 156) enriched pathways involving inflammation, cytokines, signal transduction and cell signalling. Of the DEGs from the ASD and TS analyses, 23 were shared, all of which were up-regulated: interaction networks of the common protein-coding genes using STRING revealed 5 central up-regulated hub genes: CCL2, ICAM1, HMOX1, MYC, and SOCS3. Applying KEGG and Reactome analysis to the 23 common genes identified pathways involving the innate immune response such as interleukin and interferon signalling pathways. These findings bring new evidence of shared immune signalling in ASD and TS brain transcriptome, to support the overlapping symptoms that individuals with these complex disorders experience.

Keywords: bioinformatics; brain; immune dysregulation; inflammation; neurodevelopmental disorders.