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Brain-Neuro-Endocrine-Immune
Interactions In Periodontal
Health and Disease
(Periodontitis).
My
research interest concerns
how
the brain regulates immune
system responses
controlling the collonization of
pathogenic dental plaque
microorganisms
in gingival pockets via
autonomic nervous and hormonal
systems, and the significance of
genetically determined and
environmentally-induced
differences in the reactivity of
these overarching immuno-regulatory
systems for resistance and
susceptibility to
periodontal disease
(periodontitis).
Periodontitis is a tissue
destructive inflammatory
condition of the tooth
supporting tissues (the
periodontium) that may lead to
tooth loss in the most severe
cases. The disease is most
likely induced by toxic oxygen
metabolites and enzymes released
from immune cells belonging to
the innate immune system, when
they fight and destroy
pathogenic dental plaque
microorganisms infecting the
gingival tissues. The increased
collonization of pathogenic
microorganisms in subgingival
dental plaque I suggest is the
consequence of an dysregulated
or missguided specific adaptive immune
response.
The background for my
research is clinical
observations and epidemiological
studies showing that
genetics and environmental factors, such as
cigarette smoking, poorly
regulated diabetes mellitus,
negative life events such as the
loss of a spouse by death,
poorly developed psychological
coping strategies to manage
negative life experiences, as
well as severe anxiety and major
depression of the melancholic
type, significantly increase the
risk of developing severe
periodontitis.
Our research findings
indicate that genetically
determined and environmentally-induced
dysregulation of
central nervous system
mechanisms involved in
peripheral immune regulation,
including those induced by
nicotine in cigarette smoke
through chronic activation of the
cholinergic nervous system, emotional stress through
chronic activation of the
hypothalamic-pituitary-adrenal
(HPA)
axis and the sympathetic nervous
system (which together comprise
the stress response system),
and insulin deficiency or poorly
regulated diabetes through
chronic activation of the HPA
axis,
may play important roles in
determining specific adaptive immune responses
controlling
the growth of subgingival pathogenic dental
plaque microorganisms and the
risk for developing
periodontitis. Our research
suggests
that periodontitis
may be a disease caused by
dysfunction of overarching immunoregulatory
mechanisms controlled by the
brain.
Published articles:
Breivik T, Gundersen Y, Gjermo
P, Opstad
PK.
(2013)
Chronic
treatment with the glucocorticoid
receptor antagonist RU486 inhibits
diabetes-induced enhancement of
experimental preiodontitis. Journal
of Periodontal Research.
In press
Breivik T, Gundersen Y, Gjermo
P, Taylor SM, Woodruff TM, Opstad
PK.
( 2011)
Oral treatment
with complement factor C5a receptor
(CD88) antagonists inhibits
experimental periodontitis in rats.Journal
of Periodontal Research
46,
643-647.
Breivik, T.,
Gundersen, Y., R., Gjermo, P.,
Fristad, I. & Opstad, P. K. (2011)
Systemic Chemical
desensitization of peptodergic
sensory neurons with
resiniferatoxin inhibits
experimental periodontitis. The
Open Dentistry Journal 5, 1-6.
Breivik, T.,
Gundersen, Y., R., Gjermo, P., von
Hörsten, S. & Opstad, P. K. (2009)
Nicotine acetylcholine receptor
activation mediates nicotine-induced
enhancement of experimental
periodontitis. Journal of
Periodontal Research 44, 297-304.
Breivik, T., Gundersen, Y., Myhrer, T., Fonnum, F. Osmundsen, H.,. Murison, R., Gjermo, P., von Hörsten, S. & Opstad, P. K. (2006) Enhanced susceptibility to periodontitis in an animal model of depression: reversed by chronic treatment with the antidepressant tianeptine. Journal of Clinical Periodontology 33, 469-477.
Breivik, T., Gundersen, Y., Osmundsen, H., Fonnum, F. & Opstad, P. K. (2006) Neonatal dexamathasone and chronic tianeptine treatment inhibit ligature-induced periodontitis in adult rats. Journal of Periodontal Research 41, 23-32.
Breivik, T. Psyke og periodontal helse (Norwegian). Odontology 2006 pp. 37-55.
Breivik, T., Gundersen, Y., Opstad, P. K., & Fonnum, F. (2005) Chemical sympathectomy inhibits periodontal disease in Fischer 344 rats. Journal of Periodontal Research 40, 325-330.
Breivik, T., Opstad, P. K. Engstad, R., Gundersen, G., Gjermo, P. & Preus, H. (2005) Soluble beta-1,3/1,6-glucan from yeast inhibits experimental periodontal disease in Wistar rats. Journal of Clinical Periodontology 32, 347-352.
Breivik, T., Gundersen, Y., Fonnum, F., Vaagnes, P. & Opstad, P. K. (2005) Chronic glycine treatment inhibits ligature-induced periodontal disease in Wistar rats. Journal of Periodontal Research 40, 43-47.
Breivik, T., Gundersen, Y., Osmundsen, H., Opstad, P. K.,. & Fonnum, F. (2005) Chronic treatment with the glutamate receptor antagonist MK-801 alters periodontal disease susceptibility. Journal of Periodontal Research, 40, 28-35.
Gundersen, Y., Vaagenes, P., Breivik, T., Fonnum, E. & Opstad, P.K. (2005) Glycine--an important neurotransmitter and cytoprotective agent. Acta Anaesthesiol Scand. 49, 1108-16. Review.
Breivik, T. Plakkbakteriene er neppe den primære årsak til periodontal sykdom (Norwegian). Nor Tannlegeforen Tid 2004;114:152-153.
Breivik, T. Utviklingen av periodontitt reguleres av sentralnervesytemet (Norwegian). NTFs Tidende 2003; 113:178-182.
Breivik, T. Rook GA. Oral treatment with SRP299 (killed Mycobacterium vaccae) inhibits experimental periodontal disease in Wistar rats. J Clin Periodontol. 2003;30:931-936
Stephan, M., Straub, RH., Breivik, T., Pabst, R., von Hörsten, S. Postnatal maternal deprivation aggravates experimental autoimmune encephalomyelitis in adult Lewis rats: reversal by chronicimipramine treatment. Int J Devel Neuroscience 2002;20:125-132.
Sluyter, F., Breivik, T., Cools, A. (2002) Manipulation in the maternal environment reverse genetically predisposed periodontitis in rats. Clin Diagn Lab Immunol.4, 931-932.
Breivik, T., Thrane, P. S., Gjermo, P., Cools, A. & Myhrer, T. (2002) Effects of hippocampal lesioning on experimental periodontal disease in Wistar rats. Journal of Periodontal Research 37, 360-365
Breivik, T., Stephan, M., Brabant, G. E., Straub, R. H., Pabst, R. & von Horsten, S. (2002) Postnatal lipopolysaccharide-induced illness predisposes to periodontal disease in adulthood. Brain, Behavior and Immunity 16, 421-438.
Hugoson A, Ljungquist B, Breivik, T. (2002) The relationship of some negative events and psychological factors to periodontal disease in an adult Swedish population 50-80 yars of age. J Clin Periodontol, 29, 247-253.
Breivik, T. and Rook GAW. (2002) Treatment with SRL 172 (heat-killed Mycobacterium vaccae) inhibits progression of established experimental periodontal disease in Wistar rats. J Period Res 37, 210-214.
Breivik, T., Thrane, P.S., Gjermo, P. & Fonnum, F. (2001) Postnatal glutamate-induced central nervous system lesions alter periodontal disease susceptibility in adult Wistar rats. Journal of Clinical Periodontology 28:904-909.
Breivik, T., Thrane, P. S., Gjermo, P., Opstad, P. K., Pabst, R. & von Horsten, S. (2001) Hypothalamic-pituitary-adrenal axis activation by experimental periodontal disease in rats. Journal of Periodontal Research 36, 295-300.
Breivik, T. & Thrane, P. S. (2001) Psychoneuroimmune interactions in periodontal disease. In Psychneuroimmunology. eds. R. Ader, L. Felten & N. Cohen. 3. edition, San Diego, CA: Academic Press, chapter 63, pp 627-644.
Breivik, T., Thrane, P. S., Gjermo, P. & Opstad, P. K. (2000) Glucocorticoid receptor antagonist RU-486 treatment reduces periodontitis in Fischer 344 rats. Journal of Periodontal Research 35, 285-290.
Breivik, T. and Rook GAW. Prevaccination with SRL 172 (heat-killed Mycobacterium vaccae) inhibits experimental periodontal disease in Wistar rats. Clin Exp Immunol, 2000; 120: 463-467.
Breivik, T., Sluyter, F., Hof, M. & Cools, A. (2000) Differential susceptibility to periodontitis in genetically selected Wistar rat lines that differ in their behavioral and endocrinological response to stressors. Behavior Genetics 30, 123-130.
Breivik, T., Opstad, P. K., Gjermo, P. & Thrane, P. S. (2000) Effects of hypothalamic-pituitary-adrenal axis reactivity on periodontal tissue destruction in rats. European Journal of Oral Science 108, 115-122.
Breivik, T., Thrane, P. S., Murison, R. & Gjermo, P. (1996) Emotional stress effects on immunity, gingivitis and periodontitis. European Journal of Oral Sciences 104, 327-334.
Breivik, T., Thrane, PS., Murison, B. Gjermo, P. (1996) Følelsesmessige belastninger og periodontitt (Norwegian).Nor Tannlegeforen Tid., 106, 582-587.
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