Prenatal betamethasone does not affect glutamatergic or GABAergic neurogenesis in preterm newborns

Abstract

Prenatal glucocorticoids (GCs) are routinely used for pregnant women in preterm labor to prevent respiratory distress syndrome and intraventricular hemorrhage in premature infants. However, the effect of antenatal GCs on neurogenesis in preterm neonates remains elusive. Herein, we hypothesized that prenatal GCs might suppress both glutamatergic and GABAergic neurogenesis in preterm rabbits and that this treatment would induce distinct changes in the expression of transcription factors regulating these developmental events. To test our hypotheses, we treated pregnant rabbits with betamethasone at E27 and E28, delivered the pups at E29 (term=32d), and assessed neurogenesis at birth and postnatal day 3. We quantified radial glia (Sox2+) and intermediate progenitor cells (Tbr2+) in the dorsal cortical subventricular zone to assess glutamatergic neuronal progenitors, and counted Nkx2.1+ and Dlx2+ cells in the ganglionic eminence to evaluate GABAergic neurogenesis. In addition, we assayed transcription factors regulating neurogenesis. We found that prenatal GCs did not affect the densities of radial glia and intermediate progenitors of glutamatergic or GABAergic neurons. The number of GABA+ interneurons in the ganglionic eminence was similar between the prenatal GC treated pups compared to untreated controls. Moreover, the mRNA expression of transcription factors, including Pax6, Ngn1/2, Emx1/2, Insm1, Dlx1, Nkx2.1, and Gsh2, were comparable between the two groups. However, there was a transient elevation in Mash1 protein in betamethasone treated pups relative to controls at birth. This data suggests that prenatal GC treatment does not significantly impact the balance of glutamatergic and GABAergic neurogenesis in premature infants.

Cerebellar Toxicity Induced by Maternal Exposure to Topical Betamethasone Prior to Fertilization in Newborn Rabbits

“…Betnovate solution -Scalp application 30 ml -Betamethasone 0.1% w/w (as Betamethasone Valerate) was topically applied on shaving area of back skin (5  5), for 2 months according to Vose et al (2014).…”

Betamethasone Toxicity Induced by Topical Maternal Exposure Prior to Fertilization in Heart of Newborn Rabbits

“…Betnovate solution -Scalp application 30ml -Betamethasone 0.1% w/w (as Betamethasone Valerate) was topically applied on shaving area of back skin (55), for 2 months according to Vose et al (2014).…”

Impaired Oligodendrocyte Development Following Preterm Birth: Promoting GABAergic Action to Improve Outcomes

“…Despite this finding in the guinea pig placenta, in humans exposure to a single course of betamethasone is not associated with an alteration in the neurosteroid synthesis enzymes 5α-reductase type 1 and 2 in the placenta ( 83 ), presumably due to the repeated vs. single course administration. Additionally, a study in rabbits using a single course of betamethasone based on the recommended human dose revealed no adverse effects of betamethasone on GABAergic and glutamatergic neurogenesis ( 84 ). However, a recent population-based retrospective cohort study in Finland has identified a significant increase in behavioral disorders in children that were exposed to a single course of betamethasone in utero ( 85 ).…”