RT Journal Article
SR Electronic
T1 Grandfathers-to-Grandsons Transgenerational Transmission of Exercise Positive Effects on Cognitive Performance
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP e2061232024
DO 10.1523/JNEUROSCI.2061-23.2024
VO 44
IS 23
A1 Cintado, Elisa
A1 Tezanos, Patricia
A1 De las Casas, Manuela
A1 Muela, Pablo
A1 McGreevy, Kerry R.
A1 Fontán-Lozano, Ángela
A1 Sacristán-Horcajada, Eva
A1 Pignatelli, Jaime
A1 de Ceballos, María L.
A1 del Hierro, María Jesús
A1 Fernández-Punzano, Julia
A1 Montoliu, Lluís
A1 Trejo, José Luis
YR 2024
UL http://www.jneurosci.org/content/44/23/e2061232024.abstract
AB Physical exercise is a robust lifestyle intervention known for its enhancement of cognitive abilities. Nevertheless, the extent to which these benefits can be transmitted across generations (intergenerational inheritance to F1, and transgenerational to F2 and beyond) remains a topic of limited comprehension. We have already shown that cognitive improvements resulting from physical exercise can be inherited from parents to their offspring, proving intergenerational effects. So, we set out to explore whether these enhancements might extend transgenerationally, impacting the F2 generation. In this study, we initially examined the behavioral traits of second generation (F2) male mice, whose grandfathers (F0) had an exercise intervention. Our findings revealed that F2 mice with physically active grandpaternal F0 progenitors displayed significantly improved memory recall, encompassing both spatial and non-spatial information when compared to their counterparts from sedentary F0 progenitors, and proving for the first time the transgenerational inheritance of physical exercise induced cognitive enhancement. Surprisingly, while F2 memory improved (as was the case with F1), adult hippocampal neurogenesis remained unchanged between experimental and control groups (unlike in F1). Additionally, our analysis of small RNA sequences in the hippocampus identified 35 differentially expressed miRNAs linked to important brain function categories. Notably, two of these miRNAs, miRNA-144 and miRNA-298, displayed a robust negative correlation with cognitive performance. These findings highlight the enduring transgenerational transmission of cognitive benefits associated with exercise, even after two generations, suggesting that moderate exercise training can have lasting positive effects, possibly orchestrated by a specific set of miRNAs that exert their influence across multiple generations.