Dexamethasone induces apoptosis in the developing rat amygdala in an age-, region-, and sex-specific manner

D. G. Zuloaga, D. L. Carbone, R. Hiroi, D. L. Chong, R. J. Handa

Research output: Contribution to journalArticlepeer-review

51 Scopus citations


Exposure to glucocorticoids (GCs) in early development can lead to long-term changes in brain function and behavior, although little is known about the underlying neural mechanisms. Perinatal exposure to GCs alters adult anxiety and neuroendocrine responses to stress. Therefore, we investigated the effects of either late gestational or neonatal exposure to the GC receptor agonist dexamethasone (DEX), on apoptosis within the amygdala, a region critical for emotional regulation. DEX was administered to timed-pregnant rat dams from gestational day 18 until parturition, or postnatal day 4-6. Offspring were sacrificed the day following the last DEX treatment, and tissue was processed for immunohistochemical detection of cleaved caspase-3, a marker for apoptotic cells. Prenatal DEX treatment significantly increased the number of cleaved caspase-3-positive cells in the amygdala of both sexes, largely due to increases within the medial and basomedial subregions. Postnatal DEX treatment also increased cleaved caspase-3 immunoreactivity within the amygdala, although effects reached significance only in the central nucleus of females. Overall, DEX induction of cleaved caspase-3 in the amygdala was greater following prenatal compared with postnatal treatment, yet in both instances, elevations in cleaved caspase-3 correlated with an increase in pro-apoptotic Bax mRNA expression. Dual-label immunohistochemistry of cleaved caspase-3 and the neuronal marker NeuN confirmed that virtually all cleaved caspase-3-positive cells in the amygdala were neurons, and a subset of these cells (primarily following postnatal treatment) expressed a GABAergic calcium-binding protein phenotype (calbindin or calretinin). Together these results indicate that early developmental GC exposure induces neuronal apoptosis within the amygdala in an age-, sex-, and region-dependent manner.

Original languageEnglish (US)
Pages (from-to)535-547
Number of pages13
StatePublished - Dec 29 2011
Externally publishedYes


  • Apoptosis
  • Dexamethasone
  • Glucocorticoid
  • Neonatal
  • Prenatal
  • Sex difference

ASJC Scopus subject areas

  • Neuroscience(all)


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