Paternal spatial training enhances offspring’s cognitive performance and synaptic plasticity in wild-type but not improve memory deficit in Alzheimer’s mice

Abstract

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

Intergenerational influence of paternal physical activity on the offspring’s brain: A systematic review and meta‐analysis

“…Six studies (Benito et al., 2018; McGreevy et al., 2019; Short et al., 2017; Yeshurun et al., 2017; Yin et al., 2013; Zhang et al., 2017) were conducted on mice and the rest three ones used rats (Mega et al., 2018; Park & Kim, 2017; Spindler et al., 2019). The age of father was almost similar from 8 to 10 weeks (Benito et al., 2018; Mega et al., 2018; Short et al., 2017; Spindler et al., 2019; Yeshurun et al., 2017; Yin et al., 2013) but just three studies (McGreevy et al., 2019; Park & Kim, 2017; Zhang et al., 2017) were different and used 15, 12, or 4 weeks animals. The condition of the study was the same in six studies that had included the same temperature and dark/light cycle with but the two other ones (Benito et al., 2018; Yeshurun et al., 2017) were done under the special condition as a combination of physical and mental exercise called environmental enrichment, moreover, in one study (Zhang et al., 2017), the spatial training were used for fathers.…”

“…The age of father was almost similar from 8 to 10 weeks (Benito et al., 2018; Mega et al., 2018; Short et al., 2017; Spindler et al., 2019; Yeshurun et al., 2017; Yin et al., 2013) but just three studies (McGreevy et al., 2019; Park & Kim, 2017; Zhang et al., 2017) were different and used 15, 12, or 4 weeks animals. The condition of the study was the same in six studies that had included the same temperature and dark/light cycle with but the two other ones (Benito et al., 2018; Yeshurun et al., 2017) were done under the special condition as a combination of physical and mental exercise called environmental enrichment, moreover, in one study (Zhang et al., 2017), the spatial training were used for fathers. Animals were kept under the environmental enrichment must do wheel running and the toys as well (in the form of tunnels, housing, and differently shaped objects) were changed in special intervals.…”

“…Just one study (McGreevy et al., 2019) assessed the expression of these factors on the other part of the brain like the dentate gyrus and all other ones just considered the hippocampal region. The memory of fear was checked in three studies (Benito et al., 2018; Short et al., 2017; Zhang et al., 2017) after foot‐shock training. Other outcomes like offspring physical activity, skull axis, weight were reported in only one or two studies.…”

“…Five studies (Short et al., 2017; Mega et al., 2018; McGreevy et al., 2019; Park & Kim, 2017; Spindler et al., 2019) assessed the spatial memory of offspring by Morris Maze Water test, and all of them report the increasing memory of offspring in the group of the exercised fathers in comparison to the sedentary ones. Three studies (Benito et al., 2018; Short et al., 2017; Zhang et al., 2017) investigate the memory of fear in offspring by using foot shock.…”

Nature of Tau-Associated Neurodegeneration and the Molecular Mechanisms

“…In the hyperhomocysteinemia rat model, spatial training stimulated dendrite ramification and spine generation with memory improvement in a CaMKII-dependent manner [ 78 ]. However, the paternal spatial training can only enhance an offspring’s cognitive performance and synaptic plasticity in wild-type mice but not improve memory deficit in AD transgenic mice [ 79 ].…”