Functional programming of the autonomic nervous system by early life immune exposure: implications for anxiety

Sominsky, L, Fuller, E, Bondarenko, E, Ong, L, Averell, L, Nalivaiko, E, Dunkley, P, Dickson, P and Hodgson, D 2013, 'Functional programming of the autonomic nervous system by early life immune exposure: implications for anxiety', PLoS One, vol. 8, no. 3, e57700, pp. 1-13.

Document type: Journal Article
Collection: Journal Articles

Title Functional programming of the autonomic nervous system by early life immune exposure: implications for anxiety
Author(s) Sominsky, L
Fuller, E
Bondarenko, E
Ong, L
Averell, L
Nalivaiko, E
Dunkley, P
Dickson, P
Hodgson, D
Year 2013
Journal name PLoS One
Volume number 8
Issue number 3
Article Number e57700
Start page 1
End page 13
Total pages 13
Publisher Public Library of Science
Abstract Neonatal exposure of rodents to an immune challenge alters a variety of behavioural and physiological parameters in adulthood. In particular, neonatal lipopolysaccharide (LPS; 0.05 mg/kg, i.p.) exposure produces robust increases in anxiety-like behaviour, accompanied by persistent changes in hypothalamic-pituitary-adrenal (HPA) axis functioning. Altered autonomic nervous system (ANS) activity is an important physiological contributor to the generation of anxiety. Here we examined the long term effects of neonatal LPS exposure on ANS function and the associated changes in neuroendocrine and behavioural indices. ANS function in Wistar rats, neonatally treated with LPS, was assessed via analysis of tyrosine hydroxylase (TH) in the adrenal glands on postnatal days (PNDs) 50 and 85, and via plethysmographic assessment of adult respiratory rate in response to mild stress (acoustic and light stimuli). Expression of genes implicated in regulation of autonomic and endocrine activity in the relevant brain areas was also examined. Neonatal LPS exposure produced an increase in TH phosphorylation and activity at both PNDs 50 and 85. In adulthood, LPS-treated rats responded with increased respiratory rates to the lower intensities of stimuli, indicative of increased autonomic arousal. These changes were associated with increases in anxiety-like behaviours and HPA axis activity, alongside altered expression of the GABA-A receptor α2 subunit, CRH receptor type 1, CRH binding protein, and glucocorticoid receptor mRNA levels in the prefrontal cortex, hippocampus and hypothalamus. The current findings suggest that in addition to the commonly reported alterations in HPA axis functioning, neonatal LPS challenge is associated with a persistent change in ANS activity, associated with, and potentially contributing to, the anxiety-like phenotype. The findings of this study reflect the importance of changes in the perinatal microbial environment on the ontogeny of physiological processes.
Subject Autonomic Nervous System
Biological Psychology (Neuropsychology, Psychopharmacology, Physiological Psychology)
DOI - identifier 10.1371/journal.pone.0057700
Copyright notice © 2013 Sominsky et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
ISSN 1932-6203
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Citation counts: TR Web of Science Citation Count  Cited 36 times in Thomson Reuters Web of Science Article | Citations
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