Trans-generational effects of parental exposure to drugs of abuse on offspring memory functions.

Recent evidence reported that parental-derived phenotypes can be passed on to the next generations. Within the inheritance of epigenetic characteristics allowing the transmission of information related to the ancestral environment to the offspring, the specific case of the trans-generational effects of parental drug addiction has been extensively studied. Drug addiction is a chronic disorder resulting from complex interactions among environmental, genetic, and drug-related factors. Repeated exposures to drugs induce epigenetic changes in the reward circuitry that in turn mediate enduring changes in brain function. Addictive drugs can exert their effects trans-generally and influence the offspring of addicted parents. Although there is growing evidence that shows a wide range of behavioral, physiological, and molecular phenotypes in inter-, multi-, and trans-generational studies, transmitted phenotypes often vary widely even within similar protocols. Given the breadth of literature findings, in the present review, we restricted our investigation to learning and memory performances, as examples of the offspring's complex behavioral outcomes following parental exposure to drugs of abuse, including morphine, cocaine, cannabinoids, nicotine, heroin, and alcohol.

Multigenerational effects of paternal spatial training are lasting in the F1 and F2 male offspring.

Recent studies on intergenerational transmission of learning and memory performances demonstrated that parental spatial training before fertilization could facilitate learning and memory in the offspring, but many questions remain unclarified. Essential issues regarding whether and how long the effects of parental training in a task can last in several generations, and whether learning a task repeated in the successive generations can enhance a load of multigenerational effects. In the present study, the spatial performances of F1 and F2 generations of male offspring of fathers or grandfathers spatially trained in the Morris Water Maze were evaluated and compared with the performance of a control sample matched for age and sex. Further, to investigate the memory process in F1 and F2 male offspring, brain-derived neurotrophic factor (BDNF), p-ERK1/2 and acetylated histone 3 lysine 14 (H3K14) expression levels in the hippocampus were analyzed. The findings showed that paternal training reduced escape latencies and increased time spent in the target quadrant by F1 and F2 male offspring. Besides, paternal spatial training repeated in two generations did not enhance the beneficial effects on offspring's spatial performances. These findings were supported by neurobiologic data showing that paternal training increased BDNF and p-ERK1/2 in the hippocampus of F1 and F2 male offspring. Furthermore, the hippocampal level of acetylated H3K14 increased in the offspring of spatially trained fathers, reinforcing the hypothesis that the augmented histone acetylation might play an essential role in the inheritance of spatial competence.

Maternal spatial training before fertilization improves the spatial learning process in female offspring.

Recent results of our team showed that parental spatial training before fertilization improves the offspring's spatial memory. However, the process of spatial learning (short-term/working and long-term memories, mnesic consolidation and procedures) in the offspring has not been fully clarified yet. Therefore, this study aimed at specifically analyzing whether maternal learning of a spatial task before fertilization can impact on the process of spatial learning in the female offspring. In the present study, 8-week-old female Wistar rats that had been spatially trained (or not) in the Morris Water Maze (MWM) were mated with conspecific standard-reared male rats, and their 4-week-old female offspring were spatially tested in the same MWM to evaluate their learning and memory processes. Results showed that the female offspring of trained mothers significantly displayed lower escape latencies, higher swimming speed, shorter total distance swum, longer percentage of time spent in the target quadrant and better localization memory in comparison to the female offspring of not trained mothers. Further, MWM performances of mothers trained and their female offspring significantly correlated. These findings indicate that the maternal spatial training before fertilization improves the spatial learning and memory consolidation process of the female offspring.

Intergenerational effect of parental spatial training on offspring learning: Evidence for sex differences in memory function.

On the basis of recent works demonstrating that environmental factors experienced by parents can affect their offspring, the present study was aimed at investigating whether the learning of a spatial memory task by parents before fertilization can facilitate the same learning in their offspring, and the role each parent can play in this transition. In the present study animals spatially trained (or not) in the Morris water maze were mated, and their 4 week-old male and female pups underwent spatial assessment in the same spatial task. Also, ERK1/2, BDNF, SYT1 and H3K14ac levels in the hippocampus of offspring were analyzed. We found that parental spatial training before fertilization facilitated the spatial learning and memory in their offspring. Interestingly, it was found that this transmission happened from fathers to their male offspring, and from mothers to their female offspring. Moreover, father's spatial training increased expression of BDNF and phosphorylated ERK1/2 specifically in the male offspring. We observed that father's spatial training increased acetylated H3K14 in male offspring's hippocampus, suggesting that histone acetylation may upregulate the expression of BDNF and phosphorylated ERK1/2 in the male offspring of father trained and thus contribute to the enhancement of spatial learning and memory.