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Behavioural changes induced by a conditional disruption of bone formation

Abstract Background: It has been shown that the brain regulates bone remodelling through sympathetic and parasympathetic nerve fibres. However, it is unclear if signals from the skeleton also influence brain functions and animal behaviours. Methods: Bone formation was conditionally disrupted by daily injections of aciclovir (10 mg/kg) to transgenic mice expressing a herpes-simplex-virus thymidine kinase under the control of the osteoblast-specific promoter of the Bglap gene. Behavioural studies were conducted after 10 weeks of treatment. Results: Transgenic mice receiving aciclovir injections showed a reduced number of osteoblasts with a concomitantly reduced trabecular bone volume density, when compared to wild-type controls that were treated identically. The general health of the animals was not severely affected, as indicated by a similar increase in body weight, similar activity profiles and similar social behaviours. However, transgenic mice showed significantly increased despair behaviour and increased adrenal gland weights. Conclusions: Specific animal behaviours can be modulated by a selective disruption of bone formation. The increased despair behaviour observed in transgenic animals indicates that these animals may be more prone to depression-related phenotypes. These findings are important in the context of the well-established clinical association between depression and reduced bone mass.