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.
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.
Trejo
J L
JL
Department of Cell Biology, Complutense University of Madrid, Madrid, Spain. jltrejo@cajal.csic.es
Cuchillo
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I
Machín
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Rúa
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C
D000315:Adrenalectomy; D000818:Animals; D000831:Animals, Newborn; D001835:Body Weight; D064092:Calbindin 1; D064026:Calbindins; D002452:Cell Count; D002454:Cell Differentiation; D018891:Dentate Gyrus / Q000166:cytology / Q000254:growth & development / Q000378:metabolism / Q000648:ultrastructure; D005260:Female; D005865:Gestational Age; D005938:Glucocorticoids / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism / Q000648:ultrastructure; D007150:Immunohistochemistry; D008856:Microscopy, Fluorescence; D008970:Molecular Weight; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D064030:S100 Calcium Binding Protein G / Q000378:metabolism*; D020665:Septum of Brain / Q000166:cytology / Q000254:growth & development / Q000378:metabolism
C576500:Calb1 protein, rat; D064092:Calbindin 1; D064026:Calbindins; D005938:Glucocorticoids; D064030:S100 Calcium Binding Protein G