Abstract
Adrenalectomy in the mature rat leads to death of granule cells in the dentate gyrus of the hippocampal formation. The mechanisms underlying this cell death have not been fully clarified: It has been considered that the granule cells require adrenal steroids for their survival, since corticosterone replacement prevents their death. However, adrenalectomy-induced loss of negative feedback also increases levels of corticotropin releasing hormone (CRH) in several limbic brain regions. CRH is known to induce neuronal death in hippocampal regions rich in CRH receptors. This study tested the hypothesis that adrenalectomy-induced granule cell death is mediated via the enhanced activation of CRH receptors. The extent of granule cell degeneration was compared among 4 groups of young adult male rats: Sham-adrenalectomy controls, adrenalectomized rats, adrenalectomized rats infused with a CRH antagonist from the onset of steroid deprivation to the time of sacrifice, and adrenalectomized rats infused with vehicle only. (9–41)-alpha-helical CRH was administered using an osmotic pump into the cerebral ventricles. Adrenalectomy led to robust granule cell degeneration, which was maximal in the suprapyramidal blade of the dentate gyrus. Infusion of the CRH antagonist in doses shown to block CRH actions on limbic neurons did not decrease the number of degenerating granule cells compared with the untreated or vehicle-infused adrenalectomized groups. Therefore, blocking the actions of CRH does not prevent adrenalectomy-induced granule cell death, consistent with a direct effect of corticoids on the survival of these neurons.
Highlights
Adrenalectomy (ADX) of the adult rat leads to degeneration of a significant proportion of granule cells in the dentate gyrus of the hippocampal formation (Sloviter et al, 1989; Sloviter et al, 1993a,b)
corticotropin releasing hormone (CRH) may play a pivotal role in ADX-induced death of dentate gyrus granule cells: First, previous studies have shown that CRH administration to the immature rat can lead to cell death in the hippocampal CA3 region, which is rich in CRH receptors during that developmental age (Baram and Ribak, 1995); in the adult rat, the dentate gyrus contains higher levels of CRH receptors (Avishai-Eliner et al, 1996)
CRH receptors and their messenger-RNA are abundant in the dentate gyrus of the adult rat (De Souza et al, 1985; Potter et al, 1994; Avishai-Eliner et al, 1996), which may provide a basis for the apparent selective loss of these cells after ADX
Summary
Adrenalectomy (ADX) of the adult rat leads to degeneration of a significant proportion of granule cells in the dentate gyrus of the hippocampal formation (Sloviter et al, 1989; Sloviter et al, 1993a,b). CRH may play a pivotal role in ADX-induced death of dentate gyrus granule cells: First, previous studies have shown that CRH administration to the immature rat can lead to cell death in the hippocampal CA3 region, which is rich in CRH receptors during that developmental age (Baram and Ribak, 1995); in the adult rat, the dentate gyrus contains higher levels of CRH receptors (Avishai-Eliner et al, 1996). CRH receptors and their messenger-RNA are abundant in the dentate gyrus of the adult rat (De Souza et al, 1985; Potter et al, 1994; Avishai-Eliner et al, 1996), which may provide a basis for the apparent selective loss of these cells after ADX
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