ИСТИНА

Early-life experience depends on style of maternal care and related modifications of regulatory gene expression in CNS. These effects can be replicated by epigenetic inheritance in number of generations of offspring (Meaney, 2005). In 129Sv mice, low mother care level is accompanied by ineffective odor learning with imitation of mother’s licking used as reinforcement (Aleksandrova et al., 2005). Since blockade of histone deacetylase was shown to improve learning in adult animals (Levenson et al., 2004), we were interested, whether the blockade of histone deacetylase by single injection sodium valproate 50 mg/kg s.c. on postnatal day (PD) 3 will affect the odor discrimination learning of 129Sv pups and their offspring. Control groups received saline on PD 3 and intact group received nothing. At postpartum days 5-6, dam maternal behavior of was examined. Pups were trained by stroking in the presence of mint odor at PD 8 and tested 24 hours later. Single valproate injection had no effect on learning of pups of first generation. Histone acetylation level was increased for about 72 hours after the injection and returned to normal level (Murray et al, 2009) before the training procedure on PD 8. However, according to Murray, this exposure has a long-lasting gender-dependent physiologically relevant effect (Murray et al, 2009). In present work, this effect led to long-term modifications of maternal behavioral phenotype, resulting in selective learning improvement in female pups of the next generation. Procedure of saline injections improved learning in the second-generation male pups, probably because the first-generation neonates received significantly more grooming from their mothers after stressful injection procedure (Johnston & Walker, 2003), and because maternal care level can be inherited epigenetically (Weaver et al., 2004). Thus, single injection of deacetylase inhibitor sodium valproate didn’t improve early learning in the first-generation neonates, but improved it in the second-generation pups.