E. Ahlbom et al., Prenatal exposure to high levels of glucocorticoids increases the susceptibility of cerebellar granule cells to oxidative stress-induced cell death, P NAS US, 97(26), 2000, pp. 14726-14730
Citations number
49
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
There is growing concern that prenatal exposure to excessive glucocorticoid
s may have deleterious effects on the development of various organs, includ
ing the nervous system. This study aimed at evaluating whether prenatal exp
osure to high levels of glucocorticoids might produce long-term effects on
neuronal cell survival. Pregnant rats were injected i.p. with 0.1 mg/kg dex
amethasone (DEX) from day 14 postconception, and cerebellar granule cells (
CGC) were prepared from 1-week-old rats from DEX-treated and control dams.
After 7 days in culture, cells were exposed to H2O2, methylmercury, or colc
hicine at concentrations known to induce apoptotic cell death. After exposu
re to H2O2 or methylmercury, both inducing oxidative stress, the number of
apoptotic cells was significantly higher in DEX- than in control-CGC Becaus
e mitochondria play a key role in apoptosis, mitochondrial function was inv
estigated, and a decrease in the threshold level of Ca2+ necessary for indu
ction of mitochondrial permeability transition, in Ca2+ accumulation rate,
and in oxygen consumption was detected in DEX-CGC. Moreover, the activity o
f the antioxidant enzyme catalase was significantly decreased in DEX-CGC. A
similar decrease in catalase activity was observed in cerebellar homogenat
e from newborn and 40-day-old DEX-rats. In conclusion, these results indica
te that prenatal exposure to high levels of glucocorticoids induces long-la
sting changes in CGC rendering them more sensitive to oxidative stress. Wit
h the increasing use of multiple doses of glucocorticoids in preterm infant
s, the possibility that prenatal exposure to excess glucocorticoids may lea
d to long-term neurological consequences becomes a relevant issue.