Brief but enough: 45-min maternal separation elicits behavioral and physiological responses in neonatal mice and changes in dam maternal behavior.

Currently, two gaps exist in the study of early stress response caused by maternal separation (MS) in rodents. Firstly, the influence of brief maternal separation (less than 1 hour) on physiological and behavioral development of offspring is still largely unexplored despite its fundamental and applied value. Secondly, little information is available on the social context of pups' ultrasonic vocalizations (USVs), one marker of stress response to MS, with a virtual absence of studies 1) comparing pups' USV rates during MS (absence of social interaction) with that of home cage (presence of social interaction) and 2) analysing the relationship between pup call composition and maternal behavior. After maternal separation (45 min/day) on postnatal days (PND) 3-7 we showed greater corticosterone levels on PND 7 and USV rates on PNDs 3 and 6 compared to home cage levels. Returning the pups to the dams led to a decrease in these measures. Dams' licking and grooming and pup investigation behaviors during the post-reunion period were higher on PND 3 and nursing levels were lower on PND 6 compared to control and MS baseline conditions. The pups' call composition also differed between these three conditions. Each type of dam behavior was characterized by a unique pattern of pup calls. Our previous research has demonstrated the numerous short- and long-term effects of repeated 45-min MS on development of 129Sv mice. Results presented here suggest the hormonal and behavioral responses described above might be early-life predictors of such effects.

Transport of Human Lactoferrin into Mouse Brain: Administration Routes and Distribution.

We studied different ways of transport of human lactoferrin to the brain of C57Bl/6 mice after its administration via different routes, analyzed its distribution in the brain, and determined the phenotype of lactoferrin-containing cells. Colocalization of lactoferrin and markers of various cell types was estimated by fluorescent immunohistochemical analysis. Lactoferrin was detected in mouse brain sections after its intranasal, sublingual, and intraperitoneal administration, but not after conjunctival administration. After intranasal administration, lactoferrin rapidly penetrated into the brain and accumulated in the cytoplasm of vascular endothelial cells in the neocortex, striatum, hippocampus, and thalamus. After application of protein solution onto fixed floating sections, highly specific binding of lactoferrin was found in the nuclei of neurons, astrocytes, and microglia cells, but not in the nuclei of endothelial cells of mouse brain.

Epigenetic Mechanisms of Long-Term Effects of Mother-Infant Relationship on Physiology and Behavior of the Offspring.

The quality of mother-infant relationship in the early postnatal period influences the neurophysiology and behavior of adult animals via epigenetic mechanisms. The most studied target of long-term effects of early life events on physiology and behavior is hypothalamic-pituitary-adrenal axis, in particular, epigenetic programming of glucocorticoid receptor gene expression. Inhibition of histone deacetylases is a tool for epigenetic modulation of nervous system plasticity. Using this approach, it was demonstrated that epigenetic mechanisms play an important role in physiological and behavioral modifications. It is also promising tool for reversing the negative effects of disturbances in the mother-infant relationship early in life. To date, however, the use of histone deacetylase inhibitors is widespread in adult animals, while studies in the early postnatal period are still scarce despite their relevance.

[Effects of histone deacetylase inhibitor sodium valproate on the physical and behavioral development of 129SV mice].

Sodium valproate is a widely used antiepileptic drug at high dosage levels, but it has been shown to produce a variety of toxic side-effects when used during perinatal period. These effects include increased risk of congenital anomalies and autism. For this reason, valproate is commonly employed in animal model of autism. Sodium valproate has multiple molecular targets including histone deacetylases. Therefore valproate can be utilized as a tool for the modulation of epigenetic modifications of the genome via inhibition of histone deacetylases. It is known that administration of sodium valproate at a dose of 50 mg/kg during early postnatal period leads to increase of the histone H3 acetylation level in the brain. The aim of the present study was to evaluate the effects of multiple valproate injections from 3rd to 6th postnatal day (50 mg/kg s.c.) on physical and sensorimotor development of 129Sv mice. The standard battery of tests was used. Our results show that valproate have no negative effect on physical development, sensorimotor function, and social behavior. The obtained results support the applicability of sodium valproate in our dosing schedule for further experimental modulation of histone acetulation level in the developing brain.

Maternal deprivation in early ontogeny impairs olfactory learning with mother's grooming imitation in 129Sv mice.

Early experience, mediated by mother's care, exerts long-term effects on the formation of behavioral phenotype. However, there are no published data on the effects of such experience on the results of early learning. We investigated the effects of maternal deprivation associated with handling in 129Sv mice during postnatal days 3-6 on the results of olfactory learning with mother's grooming imitation used as the reinforcement on postnatal day 8. Mother deprivation and handling procedure are shown to impair early olfactory learning.