Hippocampal neurogenesis is not enhanced by lifelong reduction of glucocorticoid levels

Abstract

Neurogenesis of dentate gyrus granule cells is generally considered to be negatively regulated by glucocorticoids. We tested the hypothesis that exposure to low plasma corticosteroid levels starting in the early postnatal period enhances granule cell proliferation rate during adulthood. Rat pups were adrenalectomized (ADX) on postnatal day 10 and were then "clamped" throughout life at low corticosterone levels via oral supplementation. Neurogenesis was determined using BrdU immunochemistry at 3 and 12 months in clamped rats as compared with age-matched, shamoperated controls. Rate of neurogenesis did not differ between the groups at either 3 or 12 months. It was significantly lower in 12-month-old compared with 3-month-old rats, despite the presence of an age-dependent increase of plasma corticosterone only in the sham-ADX rats. Granule cell layer volume, granule cell density, and granule cell degeneration (determined using apoptotic markers) were indistinguishable in the two groups, further supporting the comparable rate of neurogenesis under differing chronic glucocorticoid levels. In addition, whereas acute deprivation of plasma glucocorticoids (adrenalectomy) in adult rats evoked a burst of granule cell neurogenesis, complete elimination of these hormones (by stopping hormone supplementation) in adult, early-life ADX/clamped rats did not. These data do not support a simple inverse relationship between chronic plasma glucocorticoid levels and granule cell neurogenesis. Specifically, chronic modulation of glucocorticoid levels commencing early in life evokes additional, adaptive, and compensatory mechanisms that contribute to the regulation of granule cell proliferation.

Adaptive peripheral immune response increases proliferation of neural precursor cells in the adult hippocampus

“…After Gould and colleagues (35)(36)(37) reported an increase in adult hippocampal neurogenesis in adrenalectomized rats, adrenal hormones were believed to quite generally suppress adult neurogenesis with some reports, including those on exercise effects on adult neurogenesis, challenging that paradigm (38,39).…”

Dietary restriction inhibits spatial learning ability and hippocampal cell proliferation in rats1

“…Because we used DAB as a chromogen, BrdU‐IR cells include newborn neurons and newborn glial cells. In a study that identified the phenotypes of BrdU‐IR cells, it was shown that the proportion of glial cells among newly born cells is approximately 10% (Brunson, Baram, & Bender, 2005). The same proportion between newborn neurons and newborn glial cells was also reported in rats under a 60% dietary restriction (Yanai, 2007).…”

Molecular mechanisms of cognitive and behavioral comorbidities of epilepsy in children

“…Corticotropin‐releasing hormone (CRH) is a neuromodulatory peptide released from hippocampal interneurons in response to stress. Early life seizures have been shown to enhance hippocampal CRH mRNA expression in adulthood (Brunson et al., 2001b), and excessive CRH (Chen et al., 2004) and early life stress (Brunson et al., 2005) have been shown to lead to reductions in dendritic length and arborization as well as progressive cognitive deficits.…”