Novel adenoviral IGF-1 administration modulates the association between depressive symptoms and aging: Does gender matter?

•Frailty phenotype underlies depressive-like symptoms in aged mice model.•Behavior linked to depression is influenced by age and gender.•IGF-1 is capable to modulate depressive-like phenotype in aged mice.•IGF-1 intramuscular gene therapy is a feasible therapeutic approach to ameliorate aged associated depression. Depression is an illness of multifactorial origin and it seems to involve the dysregulation of many physiological processes. It also has been associated with age and a decreased in the expression of some neurotrophins. However, there are not unique animal models to assay depressive-like behavior, with male and females responding differently. In this study, we report the effects of gender on aged associated depressive signs as frailty, muscular strength and motor activity, as well as the role of intramuscular IGF-1 gene therapy in these processes. We found that male mice had higher general discomfort than females. Moreover, we observed that IGF-1 treatment did not modify this index in females. Regarding male mice, adenoviral IGF-1 injection reduced frailty scores compared to its adenoviral control. According to data, IGF-1 gene therapy had a positive effect on depressive associated hypo-locomotion activity as indicate by delta of total distance and the increment observed in time of mobility in male mice. This neurotrophic factor also increased the latency of time to fall in grip strength in male mice compared to female mice. Moreover, we observed that, while the therapy had no effect on the digging behavior, IGF-1 treatment diminished the latency to dig and increase the number of buried marbles in male mice, having no effect on female. The present study demonstrates that, in order to establish an animal model of depression both, gender and age are relevant variables/factors to consider. We also conclude that a frailty phenotype underlies depressive-like symptoms in an experimental mouse model. Furthermore, we demonstrated that intramuscular injection represents a less invasive, feasible and controllable route of IGF-1 gene delivery for the treatment of the depressive phenotype in old mice.