TY - JOUR
T1 - The negative impact of single prolonged stress (SPS) on bone development in mice
AU - Yu, Hongrun
AU - Watt, Heather
AU - Kesavan, Chandrasekhar
AU - Mohan, Subburaman
N1 - Funding Information:
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper. This work was funded through the Merit Review Program of the Department of Veterans Affairs, and was performed at research facilities provided by the Jerry L. Pettis Memorial VA Medical Center.
PY - 2013/9
Y1 - 2013/9
N2 - Posttraumatic stress disorder (PTSD) disrupts hypothalamic-pituitary- adrenal (HPA) axis function. Given the established role of HPA axis hormones in regulating bone metabolism, we tested the hypothesis that traumatic stress has a negative impact on bone development. We employed a variant single prolonged stress (SPS) model in which several stressors were applied to three week old C57BL/6J mice. Compared to the controls, the stressed mice showed increased freezing behavior reminiscent of PTSD symptoms. At two weeks, bone mineral content (BMC), bone area (B area) and bone mineral density (BMD) in total body based on dual-energy X-ray absorptiometry (DXA) analysis were reduced by 10.2%, 7.0% and 3.6%, respectively. Micro-CT analysis of the metaphyseal region of the excised tibia revealed that SPS caused a deterioration of trabecular architecture with trabecular number (Tb.N), BV/TV, connectivity density (Conn-Den) decreasing 12.0%, 18.9%, 23.3% and trabecular spacing (Tb.Sp), structure model index (SMI) increasing 13.9%, 21.8%, respectively. Mechanical loading increased the cross-sectional area in the mid-shaft region of the loaded right versus unloaded left tibia by 7.6% in the controls, and 10.0% in the stressed mice. Therefore, SPS applied to pre-pubertal young mice produced strong negative impact on both bone mass acquisition and trabecular architecture. Mechanical loading can be employed to increase bone size, a parameter related to bone strength, in normal as well as stressed conditions.
AB - Posttraumatic stress disorder (PTSD) disrupts hypothalamic-pituitary- adrenal (HPA) axis function. Given the established role of HPA axis hormones in regulating bone metabolism, we tested the hypothesis that traumatic stress has a negative impact on bone development. We employed a variant single prolonged stress (SPS) model in which several stressors were applied to three week old C57BL/6J mice. Compared to the controls, the stressed mice showed increased freezing behavior reminiscent of PTSD symptoms. At two weeks, bone mineral content (BMC), bone area (B area) and bone mineral density (BMD) in total body based on dual-energy X-ray absorptiometry (DXA) analysis were reduced by 10.2%, 7.0% and 3.6%, respectively. Micro-CT analysis of the metaphyseal region of the excised tibia revealed that SPS caused a deterioration of trabecular architecture with trabecular number (Tb.N), BV/TV, connectivity density (Conn-Den) decreasing 12.0%, 18.9%, 23.3% and trabecular spacing (Tb.Sp), structure model index (SMI) increasing 13.9%, 21.8%, respectively. Mechanical loading increased the cross-sectional area in the mid-shaft region of the loaded right versus unloaded left tibia by 7.6% in the controls, and 10.0% in the stressed mice. Therefore, SPS applied to pre-pubertal young mice produced strong negative impact on both bone mass acquisition and trabecular architecture. Mechanical loading can be employed to increase bone size, a parameter related to bone strength, in normal as well as stressed conditions.
KW - Bone mineral content
KW - Electric shocks
KW - Forced swimming
KW - Freezing
KW - PTSD
KW - Restraining
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U2 - 10.3109/10253890.2013.806908
DO - 10.3109/10253890.2013.806908
M3 - Article
SN - 1025-3890
VL - 16
SP - 564
EP - 570
JO - Stress
JF - Stress
IS - 5
ER -