Perinatal dexamethasone-induced alterations in apoptosis within the hippocampus and paraventricular nucleus of the hypothalamus are influenced by age and sex

Damian G. Zuloaga, David L. Carbone, Alicia Quihuis, Ryoko Hiroi, David L. Chong, Robert J Handa

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Exposure to high levels of glucocorticoids (GCs) during development leads to long-term changes in hypothalamic-pituitary-adrenal (HPA) axis regulation, although little is known about the neural mechanisms that underlie these alterations. In this study, we investigated the effects of late gestational (days 18-22) or postnatal (days 4-6) administration of the GC receptor agonist dexamethasone (DEX) on an apoptosis marker in two brain regions critical to HPA axis regulation, the hippocampus and the hypothalamic paraventricular nucleus (PVN). One day after the final DEX injection, male and female rats were sacrificed, and brains were processed for immunohistochemical detection of cleaved caspase-3, an apoptotic cell death indicator. DEX increased cleaved caspase-3 immunoreactivity in the CA1 hippocampal region of both sexes following prenatal but not postnatal treatment. Prenatal DEX also increased caspase-3 immunoreactivity in the CA3 region, an elevation that tended to be greater in females. In contrast, postnatal DEX resulted in a much smaller, albeit significant, induction in CA3 caspase-3 compared with prenatal treatment. Quantitative real-time PCR analysis revealed that prenatal but not postnatal DEX-induced hippocampal cleaved caspase-3 correlated with elevated mRNA of the proapoptotic gene Bad. Few caspase-3-ir cells were identified within the PVN regardless of treatment age, although postnatal but not prenatal DEX increased this number. However, the region immediately surrounding the PVN (peri-PVN) showed significant increases in caspase-3-ir cells following pre- and postnatal DEX. Together these findings indicate that developmental GC exposure increases apoptosis in HPAaxis-associated brain regions in an age- and sex-dependent manner.

Original languageEnglish (US)
Pages (from-to)1403-1412
Number of pages10
JournalJournal of Neuroscience Research
Volume90
Issue number7
DOIs
StatePublished - Jul 2012

Fingerprint

Paraventricular Hypothalamic Nucleus
Dexamethasone
Hypothalamus
Hippocampus
Caspase 3
Apoptosis
Glucocorticoids
Brain
Hippocampal CA1 Region
Glucocorticoid Receptors
Real-Time Polymerase Chain Reaction
Cell Death
Therapeutics
Messenger RNA
Injections

Keywords

  • Cell death
  • Glucocorticoid
  • Hypothalamic pituitary adrenal axis
  • Sex difference

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Cite this

Perinatal dexamethasone-induced alterations in apoptosis within the hippocampus and paraventricular nucleus of the hypothalamus are influenced by age and sex. / Zuloaga, Damian G.; Carbone, David L.; Quihuis, Alicia; Hiroi, Ryoko; Chong, David L.; Handa, Robert J.

In: Journal of Neuroscience Research, Vol. 90, No. 7, 07.2012, p. 1403-1412.

Research output: Contribution to journalArticle

Zuloaga, Damian G. ; Carbone, David L. ; Quihuis, Alicia ; Hiroi, Ryoko ; Chong, David L. ; Handa, Robert J. / Perinatal dexamethasone-induced alterations in apoptosis within the hippocampus and paraventricular nucleus of the hypothalamus are influenced by age and sex. In: Journal of Neuroscience Research. 2012 ; Vol. 90, No. 7. pp. 1403-1412.
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