Os hormônios tireoidianos e a hiperatividade locomotora em camundongos expostos ao etanol durante o desenvolvimento

Abstract

Ethanol consumption during pregnancy leads to a number of neurobehavioral deficits in the offspring collectively termed fetal alcohol spectrum disorder (FASD). Locomotor hyperactivity is one the most common disturbances in FASD. Besides direct damage to the nervous system, exposure to ethanol during development can also reduce thyroid hormones levels. Thyroid hormones are critical for the normal development of the nervous system, thus it is possible that changes in the levels of these hormones could contribute to the manifestation of locomotor hyperactivity frequently observed in individuals exposed to ethanol during development. This study was designed to investigate whether: 1) Ethanol exposure during the brain growth spurt, a third trimester equivalent of human gestation, decreases the levels of thyroid hormones; 2) The effects of ethanol exposure on thyroid function persist until adolescence or adulthood; and 3) Thyroxine administration is able to reduce locomotor hyperactivity in juvenile mice exposed to ethanol early during postnatal development. Each issue was investigated in a separate study. In the first study, Swiss mice received intraperitoneal (ip) injections of ethanol (ETOH group, 5 μl/g) or saline (SAL group) every other day from postnatal day 2 (PN2; PN1 = day of birth) to PN8 and the plasmatic levels of thyroid hormones were measured at PN11. In the second study, the plasmatic levels of thyroid hormones of mice from the ETOH and SAL groups were measured at PN30, PN60 or PN90. In the third study, mice from ETOH group received, at PN3, PN5, PN7 and PN9, ip injections of thyroxine (ETOH+T4; 0.4μg/100g), saline (ETOH+VEH) or were not manipulated (ETOH), whereas animals from the CONT group received saline ip injections (SAL+VEH) or were not manipulated (SAL). A group of naïve mice (NORMAL) were included in the analysis. At PN30, locomotor activity was assessed for 10 min in the open field. The first study showed that ethanol exposure significantly reduced triiodothyronine (T3) levels at PN11 but did not affect thyroxine (T4) levels. The second study showed that the reduction in T3 levels observed in the ETOH group persists until PN30, but is no longer observed at PN60 and PN90. In contrast, the levels of T4 in the ETOH group were reduced at PN30, increased at PN60 and not altered at PN90. The third study showed that locomotor activity of the ETOH+VEH, ETOH and SAL+VEH groups were higher than those of the SAL and NORMAL groups. Interestingly, no differences regarding locomotor activity were observed between SAL, NORMAL and ETOH+T4 groups. Taken together, our data suggest that ethanol exposure during the brain growth spurt period reduces the levels of thyroid hormones. This reduction could program thyroid function, changing the levels of thyroid hormones during adolescence and adulthood, and could contribute to the manifestation of the locomotor hyperactivity observed in FASD. Finally, it was shown that treatment with T4 is able to minimize the deleterious effects caused by ethanol exposure during the neonatal period.