Recent studies suggest that spatial training can maintain associative memory capacity in Tg2576 mice, but it is not known whether the beneficial effects can be inherited from the trained fathers to their offspring. Here, we exposed male wild-type and male 3XTg Alzheimer disease (AD) mice (3-m old) respectively to spatial training for one week and assessed the transgenerational effects in the F1 offspring when they were grown to 7-m old. We found that the paternal spatial training significantly enhanced progeny's spatial cognitive performance and synaptic transmission in wild-type mice. Among several synapse-or memory-associated proteins, we observed that the expression level of synaptotagmin 1 (SYT1) was significantly increased in the hippocampus of the paternally trainedoffspring. Paternal training increased histone acetylation at the promoter of SYT1 in both fathers' and the offspring's hippocampus, and as well as in the fathers' sperm. Finally, paternal spatial training for one week did not improve memory and synaptic plasticity in 3XTg AD F1 offspring. Our findings suggest paternal spatial training for one week benefits the offspring's cognitive performance in wild-type mice with the mechanisms involving an enhanced transgenerational histone acetylation at SYT1 promoter.
Physical training1-4 and mental 5-8 or physiological stimulations 9 to parents not only influence the individuals per se 1, 2, 4, 10 , but also affect the behavioral performance, emotion, and cognitive functions of their children [5][6][7]9 . For example, paternal odor fear conditioning enhances the offspring's behavioral sensitivity to the F0-conditioned smell with an increasing neuroanatomical manifestation of the Olfr151 pathway 9 . In human, maternal tristimania during pregnancy augments risk of psychiatric disorders in the offspring, especially in female fetuses 11 . In an animal study, fathers' MSUS (maternal separation combined with maternal stress) improves goal-directed behaviors and behavioral flexibility in the adult offspring, and this effect is demonstrated by epigenetic transformations including histone posttranslational modifications at the mineralocorticoid receptor (MR) gene promoter and decreased MR expression in the hippocampus 12 . However, the sole effects of fathers' experience on offspring have seldom been studied.Alzheimer's disease (AD) is the most common neurodegenerative disorder characterized pathologically by amyloidogenesis and neurofibrillary degeneration 13,14 and clinically memory deterioration started by spatial memory loss 15,16 . To date, there is no efficient cure for this devastating disorder. Recent studies suggest that spatial training can maintain associative memory capacity with enhancement of dendrite ramification and spine