title: 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. These data suggest that prenatal GC treatment does not significantly impact the balance of glutamatergic and GABAergic neurogenesis in premature infants.
authors.affiliation: Department of Pediatrics, New York Medical College-Westchester Medical Center, Valhalla, NY, United States.
authors.forename: L R
authors.initials: LR
authors.lastname: Vose
authors.affiliation: Department of Pediatrics, New York Medical College-Westchester Medical Center, Valhalla, NY, United States.
authors.forename: G
authors.initials: G
authors.lastname: Vinukonda
authors.affiliation: Department of Pediatrics, New York Medical College-Westchester Medical Center, Valhalla, NY, United States.
authors.forename: D
authors.initials: D
authors.lastname: Diamond
authors.affiliation: Department of Pediatrics, New York Medical College-Westchester Medical Center, Valhalla, NY, United States.
authors.forename: R
authors.initials: R
authors.lastname: Korumilli
authors.affiliation: Department of Pediatrics, New York Medical College-Westchester Medical Center, Valhalla, NY, United States.
authors.forename: F
authors.initials: F
authors.lastname: Hu
authors.affiliation: Department of Pediatrics, New York Medical College-Westchester Medical Center, Valhalla, NY, United States.
authors.forename: M T K
authors.initials: MT
authors.lastname: Zia
authors.affiliation: Department of Neurological Surgery, University of Washington, Seattle, WA, United States.
authors.forename: R
authors.initials: R
authors.lastname: Hevner
authors.affiliation: Department of Pediatrics, New York Medical College-Westchester Medical Center, Valhalla, NY, United States; Department of Cell Biology and Anatomy, New York Medical College-Westchester Medical Center, Valhalla, NY, United States. Electronic address: pballabh@msn.com.
authors.forename: P
authors.initials: P
authors.lastname: Ballabh
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D001623:Betamethasone / Q000009:adverse effects / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000254:growth & development / Q000502:physiology; D063928:Ependymoglial Cells / Q000187:drug effects / Q000502:physiology; D059330:GABAergic Neurons / Q000187:drug effects* / Q000502:physiology; D005938:Glucocorticoids / Q000009:adverse effects / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism*; D006128:Growth / Q000187:drug effects; D020547:Lateral Ventricles / Q000187:drug effects / Q000254:growth & development / Q000502:physiology; D058953:Neural Stem Cells / Q000187:drug effects / Q000502:physiology; D055495:Neurogenesis / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D005938:Glucocorticoids; D012333:RNA, Messenger; D014157:Transcription Factors; D018698:Glutamic Acid; D001623:Betamethasone
keywords: GABAergic; betamethasone; glucocorticoid; glutamatergic; neurogenesis; prematurity
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