Chronic Psychosocial Stress Impairs Bone Homeostasis: A Study in the Social Isolation Reared Rat

Abstract

Chronic psychosocial stress is a key player in the onset and aggravation of mental diseases, including psychosis. Although a strong association between this psychiatric condition and other medical co-morbidities has been recently demonstrated, few data on the link between psychosis and bone homeostasis are actually available. The aim of this study was to investigate whether chronic psychosocial stress induced by 4 or 7 weeks of social isolation in drug-naïve male Wistar rats could alter bone homeostasis in terms of bone thickness, mineral density and content, as well as markers of bone formation and resorption (sclerostin, cathepsin K, and CTX-I). We found that bone mineral density was increased in rats exposed to 7 weeks of social isolation, while no differences were detected in bone mineral content and area. Moreover, 7 weeks of social isolation lead to increase of femur thickness with respect to controls, suggesting the development of a hyperostosis condition. Isolated rats showed no changes in sclerostin levels, a marker of bone formation, compared to grouped animals. Conversely, bone resorption markers were significantly altered after 7 weeks of social isolation in terms of decrease in cathepsin K and increase of CTX-I. No alterations were found after 4 weeks of isolation rearing. Our observations suggest that chronic psychosocial stress might affect bone homeostasis, more likely independently from drug treatment. Thus, the social isolation model might help to identify possible new therapeutic targets to treat the burden of chronic psychosocial stress and to attempt alternative therapy choices.

Visceral Fat Dysfunctions in the Rat Social Isolation Model of Psychosis

“…Although some studies point toward a crucial role of Nox4 enzymes in adipose tissue dysfunctions, as well as metabolic disorders ( Le Lay et al, 2014 ), this has been mainly related to the weight gain associated with this conditions ( Jiang et al, 2011 ). Importantly, in this work, we showed the lack of significant differences in body weight gain between isolated and grouped animals, confirming what previously reported ( Schiavone et al, 2016 ). Hence, this could account for the absence of Nox4 alterations in the visceral fat of isolated animals.…”

“…The social isolation protocol was performed as previously described ( Schiavone et al, 2016 ). Briefly, one male and two females were housed together for mating ( Leng et al, 2004 ).…”

“…At the end of the social isolation period, in vivo dual energy X-ray absorptiometry analysis (DEXA) was performed as previously described ( Schiavone et al, 2016 ) with a body scan densitometer (Hologic Dexa Bone Densitometer, Hologic Italia S.R.L., Rome, Italy). Briefly, before measurements, body calibration scan was performed with the Hologic phantom for small animals.…”

Chronic psychosocial stress disturbs long-bone growth in adolescent mice

“…Given the striking differences between the CSC paradigm and other chronic stress models in terms of behavioral and physiological effects, we hypothesize that the CSC-induced PTSD phenotype does not induce a decrease in bone mass but rather affects bone length. Consistent with this hypothesis, rats exposed to 4-7 weeks of psychosocial isolation stress during rearing displayed increased bone mass and mineralization ( Schiavone et al, 2016 ). Therefore, in the current study, we investigated whether or not the CSC paradigm affects bone homeostasis and growth in adolescent mice, and how this might be mechanistically mediated.…”

Effects of early life stress on bone homeostasis in mice and humans

“…Stress alters their expression, and they can also act as direct and indirect growth factors for osteoblasts [14][15][16][17][18][19][20][21][22][23][24][25][26]. Latest studies indicate that psychosocial stress can lead to structural and functional changes in neuronal plasticity, neuronal marker expression, mitochondria and inflammation [4,27,28], possibly resulting in downstream alterations of bone homeostasis [29][30][31][32][33].…”