Influence of antenatal synthetic glucocorticoid administration on pyramidal cell morphology and microtubule-associated protein type 2 (MAP2) in rat cerebrocortical neurons

Abstract

Abstract.Previous animal studies have indicated that excessive prenatal circulating glucocorticoid (GC) levels induced by the antenatal administration of synthetic GC (sGC) significantly alter neuronal development in the cerebellar and hippocampal neurons of the offspring. However, it is unknown whether antenatal sGC administration results in long-term neocortical pyramidal cell impairment. In the current study, we examined whether an equivalent therapeutic dose of antenatal betamethasone phosphate (BET) in pregnant rats alters the Golgi-stained basilar dendritic length and histochemical expression of dendritic microtubule-associated protein 2 (MAP2) of neocortical pyramidal cells in infant, adolescent, and young adult offspring. The results obtained showed that in utero BET exposure resulted in a significant reduction in the basilar dendritic length per neuron and a transient reduction in histochemical MAP2 immunoreactivity. Consistent with previous hippocampal and cerebellar data, the present findings suggest that prenatal BET administration alters the dendritic growth of cerebrocortical pyramidal cells.

Environmental enrichment reverses cerebellar impairments caused by prenatal exposure to a synthetic glucocorticoid

“…The CON and CON-EE mothers were administered an equal volume (1 mL) of saline [36] . Behavioural and neuronal assessments were conducted only using male animals to avoid the effect of sex [6] , [9] , [10] , [14] , [36] . After weaning (P21), the males were separated (from the mother and the female progeny).…”

“…The progeny of 8 mothers were randomly distributed into four groups as follows: 2 progenies whose mother received BET prenatally (BET); 2 progenies who received EE postnatally and whose mother received BET prenatally (BET-EE); 2 progenies whose mother received saline prenatally (CON); and 2 progenies who received EE postnatally and whose mother received saline prenatally (CON-EE). All groups were assessed on postnatal Day 52 (P52), since this day has been considered by several authors and in our previous studies to be equivalent to the period of adolescence [6] , [9] , [10] , [12] , [14] , [36] .…”

“…Synthetic glucocorticoid (SGC) administration is considered a type of prenatal stress (PS) because it causes impaired foetal development and vulnerability to different diseases established by foetal programming, which are manifested later in adolescence or adult life [1] – [14] . Moreover, exposure to SGCs in utero during the last quarter of gestation is a pharmacological therapy widely used in the obstetric clinic to accelerate the maturation of lung tissue and subsequently increase the survival of the foetus in cases of premature birth and their use (a single course of betamethasone or dexamethasone) to mature the foetal lung in pregnancies likely to deliver before 34 weeks is recommended [3] , [6] , [8] , [11] , [14] , [15] – [17] .…”

“…In fact, surgical cerebellar resections can change the social behavior, cognition, and emotional responses of the patients [30] , [32] . Moreover, the cerebellum is highly vulnerable to exposure to SGCs, causing neuronal degeneration that underlies the cognitive and behavioural side effects that may occur during treatment with SGCs [14] , [28] , [33] – [35] . However, researchers have not yet determined whether prenatal exposure to SGCs alters the expression of GR in the cerebellum and whether these changes are manifested during postnatal life.…”

“…We systematically studied the effect of the prenatal administration of an SGC, betamethasone (BET), on some relevant aspects of neurodevelopment using Sprague-Dawley rats as an animal model [6] , [7] , [9] , [10] , [12] , [14] , [36] . Among the most relevant findings, we found that the prenatal administration of BET alters the dendritic growth of Purkinje cells [7] .…”