Natural glucocorticoid hydrocortisone was suggested as a potent substitution for dexamethasone in the treatment of bronchopulmonary dysplasia in neonates. The aim of this study was to investigate whether hydrocortisone is able to affect the expression of apoptotic genes and the intensity of naturally occurring cell death in the developing rat hippocampus. Hormone treatment decreased procaspase-3 and active caspase-3 levels as well as DNA fragmentation intensity in the hippocampal formation of one-week-old rats in 6 h after injection. These changes were accompanied by an upregulation of antiapoptotic protein Bcl-XL, while expression of proapoptotic protein Bax remained unchanged. The action of hydrocortisone was glucocorticoid receptor-independent, as the selective glucocorticoid receptor agonist dexamethasone did not affect either apoptotic protein levels or DNA fragmentation intensity in the hippocampal region. The data are the first evidences for in vivo antiapoptotic effects of hydrocortisone in the developing hippocampus., P. N. Menshanov, ... [et al.]., and Obsahuje seznam literatury
In the developing brain, mature brain derived neurotrophic factor (mBDNF) and its precursor (proBDNF) exhibit prosurvival and proapoptotic functions, respectively. However, it is still unknown whether mBDNF or proBDNF is a major form of neurotrophin expressed in the immature brain, as well as if the level of active caspase -3 correlates with the levels of BDNF forms during normal brain development. Here we found that both proBDNF and mBDNF were expressed abundantly in the rat brainstem, hippocampus and cerebellum between embryonic day 20 and postnatal day 8. The levels of mature neurotrophin as well as mBDNF to proBDNF ratios negatively correlated with the expression of active caspase -3 across brain regions. The immature cortex was the only structure, in which proBDNF was the major product of bdnf gene, especially in the cortical layers 2-3. And only in the cortex, the expression of BDNF precursor positive ly correlated with the levels of active caspase -3. These findings suggest that proBDNF alone may play an important role in the regulation of naturally occurring cell death during cortical development., P. N. Menshanov, D. A. Lanshakov, N. N. Dygalo., and Obsahuje bibliografii