The effects of hibernation and forced disuse (neurectomy) on bone properties in arctic ground squirrels.

Bone loss is a well-known medical consequence of disuse such as in long-term space flight. Immobilization in many animals mimics the effects of space flight on bone mineral density. Decreases in metabolism are also thought to contribute to a loss of skeletal mass. Hibernating mammals provide a natural model of disuse and metabolic suppression. Hibernating ground squirrels have been shown to maintain bone strength despite long periods of disuse and decreased metabolism during torpor. This study examined if the lack of bone loss during torpor was a result of the decrease in metabolic rate during torpor or an evolutionary change in these animals affording protection against disuse. We delineated changes in bone density during natural disuse (torpor) and forced disuse (sciatic neurectomy) in the hind limbs of the arctic ground squirrel (AGS) over an entire year. We hypothesized that the animals would be resistant to bone loss due to immobilization and disuse during the winter hibernation season when metabolism is depressed but not the summer active season. This hypothesis was not supported. The animals maintained bone density (dual-energy X-ray absorptiometry) and most bone structural and mechanical properties in both seasons. This was observed in both natural and forced disuse, regardless of the known metabolic rate increase during the summer. However, trabecular bone volume fraction (microcomputed tomography) in the distal femur was lower in neurectomized AGS at the study endpoint. These results demonstrate a need to better understand the relationship between skeletal load (use) and bone density that may lead to therapeutics or strategies to maintain bone density in disuse conditions.

Allopregnanolone levels and symptom improvement in severe premenstrual syndrome.

Allopregnanolone is a neuroactive metabolite of progesterone and a barbiturate-like modulator of central gamma-aminobutyric acid receptors that modify a range of behaviors, including the stress response. The aim of this study was to determine the association of allopregnanolone levels with improvement of mood and behavioral symptoms following antidepressant treatment for severe premenstrual syndrome. A second exploratory aim was to determine whether allopregnanolone levels differed between antidepressant and placebo treatments. Serum samples from 46 women who were treated with sertraline, desipramine, or placebo in double-blind conditions were assayed. Improvement was assessed as the percent change from the pretreatment baseline in premenstrual symptoms, which were rated daily by the subjects. Twenty-seven samples were from improved subjects and 19 samples were from unimproved subjects following 2 to 3 months of double-blind treatment. Posttreatment allopregnanolone levels were significantly lower in the improved compared with the unimproved subjects. Improvement was also significantly associated with lower allopregnanolone levels for premenstrual depression and appetite changes. Improvement remained significantly associated with lower allopregnanolone levels after adjustment for treatment, cycle day of blood draw, age, and the interaction of treatment and cycle day. These preliminary results offer the first placebo-controlled evidence of association between allopregnanolone levels and premenstrual syndrome treatment response and suggest the importance of further study of the associations of allopregnanolone with premenstrual syndromes and the role of allopregnanolone in response to antidepressant medications.