Glucocorticoids are popular hormones to measure in both biomedical and ecological studies of stress. Many assumptions used to interpret glucocorticoid results are derived from biomedical data on humans or laboratory rodents, but these assumptions often fail for wild animals under field conditions. We discuss five common assumptions often made about glucocorticoids in ecological and conservation research that are not generally supported by the literature. (1) High acute elevations of glucocorticoids indicate an animal in distress. In fact: because glucocorticoids are needed to survive stressors, elevated concentrations often reflect adequate coping. (2) Low glucocorticoid concentrations indicate a healthy animal. In fact: because glucocorticoids are important in responding to stressors, low glucocorticoid concentrations might indicate the lack of adequate coping. (3) Sustained elevated glucocorticoids indicate chronically stressed animals. In fact: glucocorticoid concentrations by themselves have no predictive value in diagnosing chronic stress. (4) Glucocorticoids mobilize energy to survive short‐term stressors such as predator attacks. In fact: glucocorticoids' primary impact on energy regulation is to remove glucose transporters from cell surfaces. Not only is this process too slow to provide short‐term energy, but glucocorticoid‐induced increases in glucose reflect decreased, not increased, glucose utilization. (5) Glucocorticoid measurements in non‐blood tissues (e.g., feces, hair, feathers, etc.) are equivalent to blood concentrations. In fact: these alternative tissues present imperfect reflections of blood concentrations, and it is blood concentrations that interact with receptors to evoke biological change. In summary, proper consideration of these common assumptions will greatly aid in interpreting glucocorticoid data from ecological and conservation studies.

Among species, larger animals tend to live longer than smaller ones, however, the opposite seems to be true for dogs—smaller dogs tend to live significantly longer than larger dogs across all breeds. We were interested in the mechanism that may allow for small breeds to age more slowly compared with large breeds in the context of cellular metabolism and oxidative stress. Primary dermal fibroblasts from small and large breed dogs were grown in culture. We measured basal oxygen consumption (OCR), proton leak, and glycolysis using a Seahorse XF96 oxygen flux analyzer. Additionally, we measured rates of reactive species (RS) production, reduced glutathione (GSH) content, mitochondrial content, lipid peroxidation (LPO) damage and DNA (8-OHdg) damage. Our data suggests that as dogs of both size classes age, proton leak is significantly higher in older dogs, regardless of size class. We found that all aspects of glycolysis were significantly higher in larger breeds compared with smaller breeds. We found significant differences between age classes in GSH concentration, and a negative correlation between DNA damage in puppies and mean breed lifespan. Interestingly, RS production showed no differences across size and age class. Thus, large breed dogs may have higher glycolytic rates, and DNA damage, suggesting a potential mechanism for their decreased lifespan compared with small breed dogs.

We have previously characterized human neuronal progenitor cells (hNP) that can adopt a retinal ganglion cell (RGC)-like morphology within the RGC and nerve fiber layers of the retina. In an effort to determine whether hNPs could be used a candidate cells for targeted delivery of neurotrophic factors (NTFs), we evaluated whether hNPs transfected with an vector that expresses IGF-1 in the form of a fusion protein with tdTomato (TD), would increase RGC survival in vitro and confer neuroprotective effects in a mouse model of glaucoma. RGCs co-cultured with hNPIGF-TD cells displayed enhanced survival, and increased neurite extension and branching as compared to hNPTD or untransfected hNP cells. Application of various IGF-1 signaling blockers or IGF-1 receptor antagonists abrogated these effects. In vivo, using a model of glaucoma we showed that IOP elevation led to reductions in retinal RGC count. In this model, evaluation of retinal flatmounts and optic nerve cross sections indicated that only hNPIGF-TD cells effectively reduced RGC death and showed a trend to improve optic nerve axonal loss. RT-PCR analysis of retina lysates over time showed that the neurotrophic effects of IGF-1 were also attributed to down-regulation of inflammatory and to some extent, angiogenic pathways. This study shows that neuronal progenitor cells that hone into the RGC and nerve fiber layers may be used as vehicles for local production and delivery of a desired NTF. Transplantation of hNPIGF-TD cells improves RGC survival in vitro and protects against RGC loss in a rodent model of glaucoma. Our findings have provided experimental evidence and form the basis for applying cell-based strategies for local delivery of NTFs into the retina. Application of cell-based delivery may be extended to other disease conditions beyond glaucoma.