Antenatal betamethasone produces protracted changes in anxiety‐like behaviors and in the expression of microtubule‐associated protein 2, brain‐derived neurotrophic factor and the tyrosine kinase B receptor in the rat cerebellar cortex

Abstract

Using classic Golgi staining methods, we previously showed that the administration of synthetic glucocorticoid betamethasone in equivalent doses to those given in cases of human premature birth generates long-term alterations in Purkinje cell dendritic development in the cerebellar cortex. In the present study, we evaluated whether betamethasone alters the immunohistochemical expression of proteins that participate in cerebellar Purkinje cell dendritic development and maintenance, including microtubule-associated protein 2 (MAP2), brain-derived neurotrophic factor (BDNF) and the tyrosine kinase B receptor (TrkB), which are located predominantly in the cerebellar molecular layer where Purkinje cell dendritogenesis occurs. Consistent with our previous Golgi stain studies, we observed that animals prenatally exposed to a single course of betamethasone showed long-term alterations in the expression of MAP2, BDNF and TrkB. Additionally, these protracted molecular changes were accompanied by anxiety-like behaviors in the elevated plus maze and marble burying tests.

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

“…Regarding the results obtained in the present study, although we observed that the reduction of MAP2 in the neocortex of animals exposed prenatally to BET is protracted (infant and adolescent rats), we did not observe significant differences when the animals reached young adulthood (P82). This transient reduction in MAP2 is consistent with our observation in previous studies carried out in cerebellar neurons at the same ontogenetic age (P52, –56%) ( 12 ). It should be noted that the mere transience of the reduction in immunohistochemical expression of MAP2 does not rule out the possibility that MAP2 underexpression changes the course of neuronal dendritic maturation and causes permanent structural dendritic developmental impairments, as observed in the current Golgi-stained layer II/III pyramidal cells.…”

“…However, it is unknown whether similar neuronal changes to pyramidal cortical cells occur during the early and late postnatal periods. Thus, in the current study, we analyzed the impact of prenatal BET administration (0.17 mg/kg) ( 11 , 12 , 13 ) on the dendritic growth of layer II/III pyramidal cells using the Golgi-stained procedure along with histochemical staining of the dendritic marker microtubule-associated protein 2 (MAP2) in infant (postnatal day 22, P22), adolescent (P52), and young adult (P82) rats.…”

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

“…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] .…”

Late gestational exposure to dexamethasone and fetal programming of abnormal behavior in Wistar Kyoto rats

“…In consideration of the literature, we hypothesized that prenatal exposure to sGC would lead to the fetal programming of abnormal mental health inclinations and PFC dysregulation. Specifically, we hypothesize changes to coping mechanisms and anxiety‐like behaviors when faced with inescapable stress (Cartier et al., 2016; Cerqueira et al., 2005; Hiroi et al., 2016; McGowan & Matthews, 2018; Pascual et al., 2015).…”