Enhanced susceptibility to periodontitis in an animal model of depression: reversed by chronic treatment with the anti-depressant tianeptine.
OBJECTIVE
To test the hypothesis that the olfactory bulbectomy model of depression in rats could influence susceptibility to ligature-induced periodontitis, and that chronic treatment with the anti-depressant drug tianeptine could attenuate this effect.


METHODS
Tianeptine was given twice daily (10 mg/kg, i.p.) during the entire experiment, starting 29 days before induction of olfactory bulbectomy and periodontitis. Olfactory bulbectomized (OB) rats and sham-operated rats were given saline in a similar manner. Periodontal disease was assessed when the ligatures had been in place for 21 days. Two hours before decapitation, rats were injected with lipopolysaccharide (LPS;100 microg/kg, i.p.) to induce a robust immune and stress response.


RESULTS
Compared with sham-operated controls, OB rats developed significantly more periodontal bone loss, exhibited characteristic behavioural responses in a novel open field test, and showed a decreased expression of glucocorticoid receptors (GRs) in the hippocampus. LPS provoked a significantly larger increase in circulating levels of the stress hormone corticosterone and the cytokine transformation growth factor (TGF)-1beta but smaller tumour necrosis factor (TNF)-alpha levels. Tianeptine treatment of OB rats significantly inhibited peridodontal bone loss, normalized behavioural responses, enhanced TGF-1beta levels, and abolished TNF-alpha decrease, but did not attenuate the increased corticosterone response and the decreased hippocampal GR expression.


CONCLUSIONS
These experimental results are consistent with an emerging literature showing that life stress, anxiety, depression, pathological grief, and poor coping behaviour may dysregulate regulatory mechanisms within the brain involved in immune regulation, and thereby alter immune responses and influence the susceptibility/resistance to inflammatory disorders.
Breivik
Torbjørn
T
Department of Periodontology, Faculty of Dentistry, University of Oslo, Oslo, Norway. tbreivik@odont.uio.no
Gundersen
Yngvar
Y
Myhrer
Trond
T
Fonnum
Frode
F
Osmundsen
Harald
H
Murison
Robert
R
Gjermo
Per
P
von Hörsten
Stephan
S
Opstad
Per Kristian
PK
D016301:Alveolar Bone Loss / Q000188:drug therapy / Q000209:etiology; D000704:Analysis of Variance; D000818:Animals; D000928:Antidepressive Agents / Q000627:therapeutic use*; D003863:Depression / Q000150:complications* / Q000188:drug therapy; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D018836:Inflammation Mediators / Q000097:blood; D008026:Ligation; D008070:Lipopolysaccharides / Q000276:immunology; D008297:Male; D020078:Neurogenic Inflammation / Q000209:etiology; D015213:Neuroimmunomodulation; D009830:Olfactory Bulb / Q000502:physiology* / Q000601:surgery; D010518:Periodontitis / Q000097:blood / Q000188:drug therapy / Q000209:etiology* / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar; D018709:Statistics, Nonparametric; D013841:Thiazepines / Q000627:therapeutic use*
D000928:Antidepressive Agents; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D013841:Thiazepines; C050504:tianeptine