IGF-1 gene therapy in aging mice: comparisons of frailty index between sexes. 11th FENS Forum of Neuroscience.

HERRERA M.; FALOMIR LOCKHART E; DOLCETTI FRANCO; BASMADJIAN M; HEREÑÚ C.; BELLINI MJ

Berlin

Congreso; 11th FENS Forum of Neuroscience; 2018

FENS Forum of Neuroscience

11th FENS Forum of Neuroscience. 7-11 de Julio 2018. Berlín, Alemania IGF-1 gene therapy in aging mice: comparisons of frailty index between sexesMacarena Lorena Herrera, Eugenia Falomir-Lockhart, Franco Juan-Cruz Dolcetti, Martín Osvaldo Basmadjian, Claudia Beatriz Hereñú and María José Bellini.We previously reported some therapeutical benefits of IGF-1 gene therapy administered intramuscularly in a brain injury model. Here we assessed the effects of gene therapy in the quantification of frailty through a clinical assessment of aging mice. The concept of frailty, which is a state of increased vulnerability to adverse health outcomes for people of the same age, was developed to explain the heterogeneity in clinical outcomes (aftermath) for older patients, so in this study we compared the relationship between frailty index scores, treatment and sexes. We performed 31-items Clinical Frailty Index (© Susan E. Howlett, 2013) and a set of behavioral tests in C57BL/6 mice of 24 months (pretreatment stage), then we divided the animals in three experimental groups for each sex and administered PBS and 2 different recombinant adenovirus (RAd-DS-Red or RAd-IGF-1) intramuscular (i.m). After 21 days, we quantify again FIs scores (post-treatment stage) and performed a wire mesh ramp test in order to assess strength. We observed a reduction of FIs in both sexes in the group administered with IGF-1 compared with the PBS group (p<0.05). However, there were no significant differences in the scores between sexes. Moreover, IGF-I gene therapy induced a significant improvement in strength performance in males compared with PBS group (p<0.05) and in females compared with RAd-DS-Red group (p<0.05). These therapeutically effects observed in aged mice could be the result of exogenous IGF-1 acting at multiple CNS regions, which encourage us to deepen the studies under this experimental model.