Expression modifiée de gènes de signalisation de l'histamine dans le trouble du spectre de l'autisme

Aperçu: G.M

Le système histaminergique (SH) a un rôle critique dans la cognition, le sommeil et d'autres comportements. Bien qu'il ne soit pas bien étudié dans le trouble du spectre de l'autisme (TSA), le SH est impliqué dans de nombreux troubles neurologiques, dont certains partagent une comorbidité avec le TSA, y compris le syndrome de Tourette (TS). 

Des études préliminaires suggèrent que l'antagonisme des récepteurs d'histamine 1-3 réduit les symptômes et les comportements spécifiques chez les personnes avec un diagnostic de TSA et les modèles animaux pertinents. En outre, le SHsert à la médiation de la neuroinflammation, qui peut être accrue dans les TSA. Ensemble, cela suggère que le SH peut également être modifié dans le TSA. 

Transl Psychiatry. 2017 May 9;7(5):e1126. doi: 10.1038/tp.2017.87.

Altered expression of histamine signaling genes in autism spectrum disorder

Wright C^1,2, Shin JH¹, Rajpurohit A¹, Deep-Soboslay A¹, Collado-Torres L¹, Brandon NJ³, Hyde TM^1,4,5, Kleinman JE^1,4, Jaffe AE^1,6,7, Cross AJ³, Weinberger DR^1,4,5,8,9.

Author information

1

Lieber Institute for Brain Development, Clinical Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA.

2

AstraZeneca Postdoc Program, Innovative Medicines and Early Development, Waltham, MA, USA.

3

AstraZeneca Neuroscience, Innovative Medicines and Early Development, Waltham, MA, USA.

4

Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, USA.

5

Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MD, USA.

6

Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.

7

Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.

8

The Solomon H. Snyder Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD, USA.

9

McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Abstract

The histaminergic system (HS) has a critical role in cognition, sleep and other behaviors. Although not well studied in autism spectrum disorder (ASD), the HS is implicated in many neurological disorders, some of which share comorbidity with ASD, including Tourette syndrome (TS). Preliminary studies suggest that antagonism of histamine receptors 1-3 reduces symptoms and specific behaviors in ASD patients and relevant animal models. In addition, the HS mediates neuroinflammation, which may be heightened in ASD. Together, this suggests that the HS may also be altered in ASD. Using RNA sequencing (RNA-seq), we investigated genome-wide expression, as well as a focused gene set analysis of key HS genes (HDC, HNMT, HRH1, HRH2, HRH3 and HRH4) in postmortem dorsolateral prefrontal cortex (DLPFC) initially in 13 subjects with ASD and 39 matched controls. At the genome level, eight transcripts were differentially expressed (false discovery rate <0.05), six of which were small nucleolar RNAs (snoRNAs). There was no significant diagnosis effect on any of the individual HS genes but expression of the gene set of HNMT, HRH1, HRH2 and HRH3 was significantly altered. Curated HS gene sets were also significantly differentially expressed. Differential expression analysis of these gene sets in an independent RNA-seq ASD data set from DLPFC of 47 additional subjects confirmed these findings. Understanding the physiological relevance of an altered HS may suggest new therapeutic options for the treatment of ASD.

PMID: 28485729

DOI: 10.1038/tp.2017.87