Efeitos do controle de temperatura e da vimpocetina sobre os déficits neurocomportamentais decorrentes do estresse por separação materna em camundongos suíços neonatos

Abstract

The stress during development is associated with several neurobehavioral disorders that can persist into postnatal life. Hyperactivity is one of these disorders that is frequently observed in humans early exposed to the early stress. This disorder may be the predominant clinical manifestation, or merge itself with attention deficit, impulsivity and impaired learning, composing the Attention Deficit Hyperactivity Disorder (ADHD), with the number of diagnosed cases on the rise. Several experimental protocols use maternal separation (MS) of newborn rodents to mimic the effects of early life stress in humans. This predilection for newborn rodents is due to its approximate equivalence with human fetuses at the 3rd trimester of pregnancy in terms of neurodevelopment, when there is the greatest growth of the fetal Central Nervous System (CNS). This work was carried out in three separate studies. In the first study, Swiss mice underwent daily sessions of isolation with maternal separation between the 2nd day of postnatal life (PN2) to PN10, varying the isolation temperature of the puppies, that were kept without heating (with the room temperature between 22 and 25° C) or heated at 37 °C during these sessions. Therefore, we had three groups: warmed isolation with MS ; unheated isolation with MS ; and control. Control group animals were weighed in PN2 and PN10 and promptly returned to its progenitors. All animals were weaned and sexed in PN21 and were tested from PN30 in the Open Field and Inhibitory Passive Avoidance. In a second study, serum basal corticosterone and thyroid hormones were measured in the three experimental groups at PN6, PN10 and PN30. Finally, in a third study, mice from the control group and the group unheated isolation with MS were treated with Vinpocetine (20g / kg), a drug with potential neuroprotective effects, or vehicle (dimethylsulfoxide), in order to evaluate the effects of Vinpocetine on locomotor activity. The 1st study showed that the temperature was critical for the manifestation of locomotor hyperactivity in the Open Field Test, since it took place only in the group submitted to the unheated isolation. There were no differences among groups in the Inhibitory Avoidance Test concerning to memory and learning. The 2nd study showed that the temperature during isolation influenced significantly the levels of basal corticosterone and thyroid hormones in PN10 and PN30. In the 3rd study, Vinpocetine reduced the locomotor hyperactivity in animals submitted to the unheated isolation. Our results suggest that the temperature during neonatal isolation is an important factor to manifestation of neuroendocrine disorders caused by early stress in mice, and that Vinpocetine was able to mitigate them, without increasing mortality. Finally, considering that many cases of hyperactivity in human children are related to prematurity, raises the hypothesis that thermal stress by cold is one of the factors involved in the pathogenesis of hyperactivity in these cases.