Neuropeptide Y Y2 antagonist treated ovariectomized mice exhibit greater bone mineral density.

Osteoporosis, a disease characterized by progressive bone loss and increased risk of fracture, often results from menopausal loss of estrogen in women. Neuropeptide Y has been shown to negatively regulate bone formation, with amygdala specific deletion of the Y2 receptor resulting in increased bone mass in mice. In this study, ovariectomized (OVX) mice were injected once daily with JNJ-31020028, a brain penetrant Y2 receptor small molecule antagonist to determine the effects on bone formation. Antagonist treated mice had reduced weight and showed increased whole-body bone mineral density compared to vehicle-injected mice. Micro computerized tomography (micro-CT) demonstrated increased vertebral trabecular bone volume, connectivity density and trabecular thickness. Femoral micro-CT analysis revealed increased bone volume within trabecular regions and greater trabecular number, without significant difference in other parameters or within cortical regions. A decrease was seen in serum P1NP, a measure used to confirm positive treatment outcomes in bisphosphonate treated patients. C-terminal telopeptide 1 (CTX-1), a blood biomarker of bone resorption, was decreased in treated animals. The higher bone mineral density observed following Y2 antagonist treatment, as determined by whole-body DEXA scanning, is indicative of either enhanced mineralization or reduced bone loss. Additionally, our findings that ex vivo treatment of bone marrow cells with the Y2 antagonist did not affect osteoblast and osteoclast formation suggests the inhibitor is not affecting these cells directly, and suggests a central role for compound action in this system. Our results support the involvement of Y2R signalling in bone metabolism and give credence to the hypothesis that selective pharmacological manipulation of Y2R may provide anabolic benefits for treating osteoporosis.

Plasticity of the electric organ discharge waveform of male Brachyhypopomus pinnicaudatus. II. Social effects.

Many electric fish produce sexually dimorphic electric organ discharges. Although electric organ discharges are comprised of action potentials, those of the Gymnotiform family Hypopomidae show significant plasticity in response to stress and time of day. We show here that male Brachyhypopomus pinnicaudatus (Hopkins 1991), adjusts the degree of sexual dimorphism in its electric organ discharge depending on immediate social conditions. Three to five days of isolation resulted in gradual decrease of two sexually dimorphic waveform characters: duration and amplitude. Introduction of a second fish to the experimental tank restored electric organ discharge duration and amplitude. Duration recovered quicker than amplitude, and both recovered faster in the presence of males than females. In studies of other electric fish species, treatment with steroid sex hormones have taken several days to increase sexual dimorphism in the electric organ discharge. The socially induced changes seen in this study are initiated too quickly to involve classic steroid action of genomic transcription and thus may depend on another mechanism. Socially induced regulation of the male's electric organ discharge waveform is consistent with the compromises in signaling strategy shown by other taxa with costly sexual advertisement signals.