Enhanced Brain Cell Proliferation Following Early Adrenalectomy in Rats

Abstract

We have previously demonstrated an increase in adult brain DNA content in rats adrenalectomized on postnatal day 11. The present studies examined cell proliferation in cerebral cortex, cerebellum, hippocampus, and midbrain-diencephalon following adrenalectomy at this age. Compared to sham-operated controls, adrenalectomized animals showed increased [3H]thymidine incorporation into DNA (measured at 1 h following a pulse injection) in all brain regions at 7 and 14 days postsurgery. In some areas, the effect was already present as early as 2 days following adrenalectomy. Chronic replacement with corticosterone prevented this increase in DNA labelling in a dose-dependent manner. When cell proliferation in the cerebral cortex and cerebellum was independently assessed by measuring changes in thymidine kinase activity, enzyme activity was significantly elevated in both areas at 7 and 14 days postsurgery. Finally, histological examination of the cerebellar cortex suggested a delayed disappearance of the external granular layer in several cerebellar lobules of adrenalectomized animals. Overall, these findings indicate that day-11 adrenalectomy leads to a prolonged stimulation of mitotic activity in areas where cell formation at this time is exclusively glial (i.e., cerebral cortex and mid-brain-diencephalon) as well as in areas where postnatal neurogenesis is also occurring (cerebellum and hippocampus). It is hypothesized that this stimulation results from the removal of a tonic inhibitory effect exerted by circulating glucocorticoids in the normal intact animal.

Current perspectives of the roles of the central norepinephrine system in anxiety and depression

“…[78][79][80] For example, corticosteroid elevation due to stress-activation of the HPA axis may suppress adult neurogenesis, especially in the hippocampal dentate gyrus, to disrupt plasticity-dependent learning and memory in the hippocampus. [81][82][83] Additionally, persistent elevation of circulating corticosteroids can also cause atrophy of other important brain regions for cognitive and emotional processes, such as the prefrontal cortex and amygdala. [84,85] As depletion of central NE leads to a decline in adult hippocampal neurogenesis, [86,87] it is likely that an elevation of NE (e.g., by antidepressants) has an indirect role in regulating BDNF-dependent adult hippocampal neurogenesis.…”

Glucocorticoid Receptor mRNA Ontogeny in the Fetal and Postnatal Rat Forebrain

“…However, the onset of GR gene expression in specific limbic structures and the localization and relative abundance of GR-mRNA in fetal rat brain have not been reported. Such information is of importance in view of the putative role of glucocorticoids (GC) in neuronal development and differentiation (4)(5)(6). This study focuses on the distribution of GR-mRNA in the fetal and neonatal rat brain, with emphasis on hypothalamic and limbic structures.…”

Glucocorticoids and circadian clock control of cell proliferation: At the interface between three dynamic systems

“…Adrenalectomy has been reported to result in reduced cell proliferation, for example in the small intestine [119][120][121], and in increased proliferation in regions of the brain ( [122,123] and see the section on neurogenesis below). Also lung cell proliferation is influenced by glucocorticoids, as revealed by studies of mice lacking the CRH peptide [124,125].…”