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The common brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is associated with reduced activity-dependent BDNF release and increased risk for anxiety disorders and PTSD. Here we behaviorally phenotyped a novel Val66Met rat model with an equivalent valine to methionine substitution in the rat Bdnf gene (Val68Met). In a three-day fear conditioning protocol of fear learning and extinction, adult rats with the Met/Met genotype demonstrated impaired fear memory compared to Val/Met rats and Val/Val controls, with no genotype differences in fear learning or extinction. This deficit in fear memory occurred irrespective of the sex of the animals and was not seen in adolescence (4 weeks of age). There were no changes in open-field locomotor activity or anxiety measured in the elevated plus maze (EPM) nor in other types of memory measured using the novel-object recognition test or Y-maze. BDNF exon VI expression in the dorsal hippocampus was higher and BDNF protein level in the ventral hippocampus was lower in female Val/Met rats than female Val/Val rats, with no other genotype differences, including in total BDNF, BDNF long, or BDNF IV mRNA. These data suggest a specific role for the BDNF Met/Met genotype in fear memory in rats. Further studies are required to investigate gene–environment interactions in this novel animal model.

Skeletal muscle weakness commonly occurs in patients with COPD. Long-term use of systemic glucocorticosteroids further contributes to muscle weakness. Anabolic steroids could be an additional mode of intervention to improve outcome of pulmonary rehabilitation by increasing physiologic functioning, possibly mediated by increasing erythropoietic function.We randomly assigned 63 male patients with COPD to receive on days 1, 15, 29, and 43 a deep IM injection of 50 mg of nandrolone decanoate (ND) [Deca-Durabolin; N.V. Organon; Oss, The Netherlands] in 1 mL of arachis oil, or 1 mL of arachis oil alone (placebo) in a double-blind design. All patients participated in a standardized pulmonary rehabilitation program. Outcome measures were body composition by deuterium and bromide dilution, respiratory and peripheral muscle function, incremental exercise testing, and health status by the St. George's Respiratory Questionnaire.Treatment with ND relative to placebo resulted in higher increases in fat-free mass (FFM; mean, 1.7 kg [SD, 2.5] vs 0.3 kg [SD, 1.9]; p = 0.015) owing to a rise in intracellular mass (mean, 1.8 kg [SD, 3.1] vs - 0.5 kg [SD, 3.1]; p = 0.002). Muscle function, exercise capacity, and health status improved in both groups to the same extent. Only after ND were increases in erythropoietic parameters seen (erythropoietin: mean, 2.08 U/L [SD, 5.56], p = 0.067; hemoglobin: mean, 0.29 mmol/L [SD, 0.73], p = 0.055). In the total group, the changes in maximal inspiratory mouth pressure (PImax) and peak workload were positively correlated with the change in hemoglobin (r = 0.30, p = 0.032, and r = 0.34, p = 0.016, respectively), whereas the change in isokinetic leg work was correlated with the change in erythropoietin (r = 0.38, p = 0.013). In the patients receiving maintenance treatment with low-dose oral glucocorticosteroids (31 of 63 patients; mean, 7.5 mg/24 h [SD, 2.4]), greater improvements in PImax (mean, 6.0 cm H(2)O [SD, 8.82] vs - 2.18 cm H(2)O [SD, 11.08], p = 0.046), and peak workload (mean, 20.47 W [SD, 19.82] vs 4.80 W [SD, 7.74], p = 0.023) were seen after 8 weeks of treatment with ND vs placebo.In conclusion, a short-term course of ND had an overall positive effect relative to placebo on FFM without expanding extracellular water in patients with COPD. In the total group, the improvements in muscle function and exercise capacity were associated with improvements in erythropoietic parameters. The use of low-dose oral glucocorticosteroids as maintenance medication significantly impaired the response to pulmonary rehabilitation with respect to respiratory muscle function and exercise capacity, which could be restored by ND treatment.

Anabolic steroids may be an additional mode of intervention to promote anabolism and improve clinical outcome in various acute and chronic wasting diseases. The present review discusses the rationale for anabolic steroid treatment in acute and chronic disease, their mechanistic actions, the available clinical trials in acute and chronic disease and their side-effects.