Maternal Deprivation of Lewis Rat Pups Increases the Severity of Experi-mental Periodontitis in Adulthood
Torbjørn Breivik 1, 2, *, Yngvar Gundersen 2, Robert Murison 3, Jonathan D Turner 4, Claude P Muller 4, Per Gjermo 1, Kristian Opstad 2
1 Department of Periodontology, Faculty of Dentistry, University of Oslo, Norway
2 Norwegian Defence Research Establishment, Division for Protection, Kjeller, Norway
3 Department of Biology and Medical Psychology, Faculty of Psychology, University of Bergen, Norway
4 Institute of Immunology, CRP- Santé/Laboratoire National de Sante, 20A Rue Auguste Lumière, L-1950, Luxembourg
Background and Objective:
Early life adverse events may influence susceptibility/resistance to chronic inflammatory diseases later in life by permanently dysregulating brain-controlled immune-regulatory systems. We have investigated the impact of infant-mother separation during early postnatal life on the severity of experimental periodontitis, as well as systemic stress and immune responses, in adulthood.
Material and Methods:
Pups of periodontitis resistant Lewis rats were separated from their mothers for 3 h daily during postnatal days 2-14 (termed maternal deprivation; MD), separated for 15 min daily during the same time period (termed handling; HD), or left undisturbed. As adults, their behaviour was tested in a novel stressful situation, and ligature-induced periodontitis applied for 21 days. Two h before sacrifice all rats were exposed to a gram-negative bacterial lipopolysaccharide (LPS) challenge to induce a robust immune and stress response.
Compared to undisturbed controls, MD rats developed significantly more periodontal bone loss as adults, whereas HD rats showed a tendency to less disease. MD and HD rats exhibited depression-like behaviour in a novel open field test, while MD rats showed higher glucocorticoid receptor (Gr) expression in the hippocampus, and HD rats had altered methylation of genes involved in the expression of hippocampal Gr. LPS provoked a significantly lower increase in circulating levels of the cytokine TGF-1β in MD and HD rats, but there were no significant differences in levels of the stress hormone corticosterone.
Stressful environmental exposures in very early life may alter immune responses in a manner that influences susceptibility/resistance to periodontitis.
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* Address correspondence to this author at the Department of Periodontology, P.O.Box 1109 Blindern, N-0317 Oslo, Norway; Tel: +47 22 85 23 56; Fax: +47 22 85 23 51; E-mail: email@example.com