Aggravating Effects of Psychological Stress on Ligature-Induced Periodontitis via the Involvement of Local Oxidative Damage and NF-κB Activation

Abstract

Periodontitis is the leading cause of tooth loss in adults, and psychological factors play an important role in the development of periodontitis. To elucidate the adverse effects of psychological stress on the inflammatory process and redox status of periodontitis tissue, fifty male Sprague-Dawley rats were divided into the control, experimental periodontitis, psychological stress, experimental periodontitis plus psychological stress, and experimental periodontitis plus psychological stress plus fluoxetine groups. Chronic unpredictable mild stress (CUMS) was used to establish psychological stress, and silk ligature was used to induce experimental periodontitis. Four weeks later, stressed rats showed altered behaviour, serum hormone levels, and sucrose preference. More obvious alveolar bone loss and attachment loss and higher protein expressions of inflammatory cytokines were observed in the experimental periodontitis plus psychological stress group. The combination of CUMS and periodontitis had synergistic effects on increasing hypoxia-inducible factor-1α (HIF-1α) protein expression and reactive oxygen species (ROS) and malondialdehyde (MDA) contents and decreasing antioxidant enzyme activities compared with those in the stress or periodontitis groups. Moreover, psychological stress further increased p-IκBα and p-NF-κB p65 protein levels and decreased IκBα protein levels in periodontitis rats. Fluoxetine administration alleviated the adverse effects of psychological stress on the progression of periodontitis in rats. These results hint us that psychological stress could aggravate inflammation in periodontitis tissues, which may be partly due to local worsening of oxidative damage and further activation of the nuclear factor kappa-B (NF-κB) signalling pathway.

Preventive effects of melatonin on periodontal tissue destruction due to psychological stress in rats with experimentally induced periodontitis

“…Various in vivo studies on the effects of restraint stress on periodontal tissue destruction are found in the literature. 7,8,15,25,[37][38][39][40] Our histomorphometric measurement results showing that restraint stress alone causes only mild bone loss while it significantly aggravates ligature-induced destruction are consistent with many previous studies conducted with a similar methodology. 7,8,15,25,[37][38][39][40] In contrast, Foureaux et al 15 reported that physical restraint does not significantly affect RANKL or OPG levels or periodontal destruction.…”

“…7,8,15,25,[37][38][39][40] Our histomorphometric measurement results showing that restraint stress alone causes only mild bone loss while it significantly aggravates ligature-induced destruction are consistent with many previous studies conducted with a similar methodology. 7,8,15,25,[37][38][39][40] In contrast, Foureaux et al 15 reported that physical restraint does not significantly affect RANKL or OPG levels or periodontal destruction. This finding of their study differing from the current study and previous studies might be explained by the short duration of exposure to immobilization (2.5 h daily for 30 days) in their study.…”

“…[3][4][5] Stress, which is inevitable in the modern world, is a psychophysical response to emotional and cognitive factors recognized as extreme by the individual. [6][7][8] Physiologic responses to stress include stimulation of the hypothalamic-pituitary-adrenal (HPA) axis and the locus coeruleus-sympathetic-adrenal medullary system (SAM).…”

“…3,4 Some physiological changes occurring under chronic stress, the foremost of which is high cortisol release, modulate immunologic, inflammatory, and oxidative processes and affect the pathogenesis of various inflammatory diseases. 3,4,7,8 Chronic stress is considered a potential risk factor for periodontitis. 3,9 Many recent studies have shown that stress and anxiety exacerbate periodontitis 6,10 and negatively affect the clinical outcomes of periodontal treatment.…”

A New Experimental Model of Periodontitis in Rats

“…Chronic stress used as a general factor in the current model stimulates the discharge of a large number of superoxide anions into the intercellular matrix thus promoting a higher degree of disorganization of periodontal connective tissue structures. Physiological reactions to chronic stress modify the immune system through nervous (autonomous nervous system) and endocrine (hypothalamic-pituitary-adrenal axis) systems [16,17].…”