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PMID: 23483921 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

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

PloS one ·Vol. 8 ·No. 3 ·2013-00-00 ·Pages e57700

Sominsky L, Fuller EA, Bondarenko E, Ong LK, Averell L, Nalivaiko E, Dunkley PR, Dickson PW, Hodgson DM

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.

MeSH Terms
Animals Animals, Newborn Anxiety/blood,immunology,physiopathology Autonomic Nervous System/immunology,physiopathology Behavior, Animal/drug effects Brain/drug effects,metabolism,pathology,physiopathology Corticosterone/blood Female Gene Expression Regulation/drug effects Lipopolysaccharides/pharmacology Male Phosphorylation/drug effects Phosphoserine/metabolism Rats Rats, Wistar Respiration/drug effects Tyrosine 3-Monooxygenase/metabolism Weight Gain/drug effects
Chemicals
Lipopolysaccharides Phosphoserine Tyrosine 3-Monooxygenase Corticosterone
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Sominsky Luba
Laboratory of Neuroimmunology, School of Psychology, The University of Newcastle, Callaghan, New South Wales, Australia. [email protected]
Fuller Erin A
Bondarenko Evgeny
Ong Lin Kooi
Averell Lee
Nalivaiko Eugene
Dunkley Peter R
Dickson Phillip W
Hodgson Deborah M
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Article Info
Journal
PloS one
Abbr.
PLoS One
ISSN
1932-6203
DOI
10.1371/journal.pone.0057700
Email
[email protected]
Published
2013-00-00
Epub
2013-00-06
Pages
e57700
Language
English
Region
United States
NLM ID
101285081
PMCID
PMC3590226
Subset
IM
External Links
PubMed source DOI: 10.1371/journal.pone.0057700 PMC Full Text View journal details
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