Strain differences in the susceptibility to the gut-brain axis and neurobehavioural alterations induced by maternal immune activation in mice.

Abstract:

:There is a growing realization that the severity of the core symptoms of autism spectrum disorders and schizophrenia is associated with gastrointestinal dysfunction. Nonetheless, the mechanisms underlying such comorbidities remain unknown. Several genetic and environmental factors have been linked to a higher susceptibility to neurodevelopmental abnormalities. The maternal immune activation (MIA) rodent model is a valuable tool for elucidating the basis of this interaction. We induced MIA with polyinosinic-polycytidylic acid (poly I:C) at gestational day 12.5 and assessed behavioural, physiological and molecular aspects relevant to the gut-brain axis in the offspring of an outbred (NIH Swiss) and an inbred (C57BL6/J) mouse strain. Our results showed that the specific MIA protocol employed induces social deficits in both strains. However, alterations in anxiety and depression-like behaviours were more pronounced in NIH Swiss mice. These strain-specific behavioural effects in the NIH Swiss mice were associated with marked changes in important components of gut-brain axis communication: the endocrine response to stress and gut permeability. In addition, MIA-induced changes in vasopressin receptor 1a mRNA expression in the hypothalamus were observed in NIH Swiss mice only. Taken together, these data suggest that genetic background is a critical factor in susceptibility to the gut-brain axis effects induced by MIA.

journal_name

Behav Pharmacol

journal_title

Behavioural pharmacology

authors

Morais LH,Felice D,Golubeva AV,Moloney G,Dinan TG,Cryan JF

doi

10.1097/FBP.0000000000000374

subject

Has Abstract

pub_date

2018-04-01 00:00:00

pages

181-198

issue

2 and 3-Spec Issue

eissn

0955-8810

issn

1473-5849

journal_volume

29

pub_type

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