Maternal adrenalectomy at the early onset of gestation impairs the postnatal development of the rat hippocampal formation: Effects on cell numbers and differentiation, connectivity and calbindin‐D28k immunoreactivity

Abstract

The possible role of the maternal glucocorticoids on the postnatal development of the hippocampus was tested with bilateral adrenalectomy of pregnant rats. Surgery was performed 24 hr after sperm-positiveness was determined. The offspring from adrenalectomized mothers, compared with animals from control sham-operated mothers, showed decreased body weight and increased brain weight. The CA1 field of the hippocampus of these animals showed lower number of both Nissl-stained and Calbindin-immunoreactive cells, whereas the granule cell layer of the dentate gyrus showed higher number of both populations. Both types of cell numbers were statistically similar from postnatal Day 21, however, suggesting some compensatory mechanism. The neuronal populations of adrenalectomized animals appeared with a delay in the development of their dendritic trees, cytoplasmic differentiation, and synaptic connections. In the same way, both septohippocampal and hippocamposeptal projections appeared delayed in the adrenalectomized animals with respect to control ones by several days, mainly with regard to regressive events typical of the first 8 days of age. The ultrastructural study showed that every ADX postnatal group appeared more immature than the corresponding control group. These results suggest that gestational levels of maternal glucocorticoids (that were removed by adrenalectomy) influence the normal postnatal development of the hippocampus as reflected in neuron numbers and cell maturation, as well as in the developmental timing of the pattern of connectivity, and that this effect must be accomplished both in neuroepithelium and post-mitotic cells before the endogenous fetal hormones are secreted and reach concentrations capable to produce a response.

The Timing of Prenatal Exposure to Maternal Cortisol and Psychosocial Stress Is Associated With Human Infant Cognitive Development

“…GCs, in addition to their critical role in lung maturation, play an important role in normal brain development and have been implicated in neuronal maturation and survival (Drake, Tang, & Nyirenda, 2007; Scaccianoce et al., 2001; Trejo et al., 2000). The association between increased concentrations of cortisol during the third trimester and improved cognitive functioning at 12 months of age is highly plausible given the role that GCs have been shown to play in regulating brain development in animal models.…”

“…GC receptors are present throughout the central nervous system (Diorio, Viau, & Meaney, 1993; Jacobson & Sapolsky, 1991; Sanchez, Young, Plotsky, & Insel, 2000) and GCs easily pass through the blood–brain barrier (Zarrow, Philpott, & Denenberg, 1970). GCs play a critical role in normal brain development, which provides further evidence for GCs as a mechanism for programming the fetus (Matthews, 2000; Trejo, Cuchillo, Machin, & Rua, 2000; Welberg & Seckl, 2001).…”

“…Furthermore, moderate increases in GCs have salutary effects on both brain development and behavioral regulation (Kapoor, Dunn, Kostaki, Andrews, & Matthews, 2006). For example, rodents exposed in the early postnatal period to moderate increases in GCs display decreased physiological and behavioral stress responses, persisting improvements on cognitive tasks assessing learning and memory, and increased neural plasticity (Catalani et al., 2002; Scaccianoce, Catalani, Lombardo, Consoli, & Angelucci, 2001; Trejo et al., 2000). Exposure to excess GCs, however, particularly during vulnerable periods, appears to be neurotoxic (Uno et al., 1990; Uno et al., 1994).…”

Dexamethasone blocks the migration of the human neuroblastoma cell line SK-N-SH

“…For example, it has been reported that Dex decreases the migration rate induced by EGF on HSC-2 cells derived from a buccal mucosa squamous cell carcinoma (27) and that Gc reduce the motility of eosinophils in nasal polyps (28). These in vitro experiments are reminiscent of in vivo studies demonstrating that Gc exert an inhibitory effect on the migration of neuronal cells during fetal life in mammals (29,33,34). In view of these findings, one may hypothesize that Gc utilized to keep under control a variety of brain tumors (35) exert their effects not only by reducing brain edema and cell proliferation but also by acting on the migratory capacity of tumor cells.…”

Exposición fetal a glucocorticoides se asocia al desarrollo cerebral en preadolescentes

“…Los efectos benéficos de los corticoides sobre la morbimortalidad fetal están bien avalados por sólida evidencia (2), pero se ha observado que los glucocorticoides también pueden afectar el desarrollo del cerebro fetal. Experimentos animales han demostrado que la exposición fetal a corticoides altera el neurodesarrollo en roedores, ovejas y primates (3)(4)(5)(6)(7)(8). Estudios en humanos han asociado el uso de corticoides antenatales con disminución del volumen y complejidad de los pliegues corticales (9,10).…”