Enhanced brain cell proliferation following early adrenalectomy in rats.

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.

Adrenalectomy in the developing rat: does it cause reduced or increased brain myelination?

We have previously demonstrated increased myelination in adult rats that were adrenalectomized (ADX) neonatally. However, Preston and McMorris (1984) recently reported reduced myelination at Day 21 or 22 in day 14 ADX animals. The present experiment attempted to replicate Preston and McMorris' study to determine whether early adrenalectomy might be producing a transient hypomyelination prior to the hypermyelination observed at later time points. We were unable to duplicate the exact protocol of Preston and McMorris (which involved weaning at Day 18 with administration of saline and glucose drinking solutions) because of 100% mortality of our ADX rats by Day 20. However, using our standard mineralocorticoid replacement therapy which allowed the animals to remain with their mothers, all of the ADX rats survived, and we were able to assess myelination in these animals by means of standard biochemical methods. All measures showed absolutely no reduction in myelination in ADX rats compared with sham-operated controls. The discrepancy between the present results and those of Preston and McMorris are attributed, at least in part, to the early weaning procedure used by these investigators.

Early adrenalectomy increases myelin content of the rat brain.

Rats were adrenalectomized (ADX) or sham-operated (SHAM) on the 11th day of life and killed on days 35-36, 63, or 151-153 for the isolation of cerebral myelin from each animal. Despite having lower overall body weights, ADX rats had heavier cerebra than SHAM control rats at all ages. Mean cerebral weight increases were 10.0% at day 35-36, 15.3% at day 63, and 16.7% at day 151-153. Recovered myelin dry weights were even more elevated in the ADX rats, but only at day 63 (41.7% increase) and 151-153 (42.1% increase). At both of these ages, there was a clear linear relationship between cerebral wet weights and the amount of myelin recovered from the cerebra. Analysis of the day-63 myelin samples showed no group differences in total cholesterol or protein concentration or in the specific activity of the myelin marker enzyme 2':3'-cyclic-nucleotide 3'-phosphodiesterase (CNP). However, myelin isolated from the ADX rats appeared to be deficient in both galactolipid and phospholipid. Optic nerve myelination was assessed in all animals by measuring CNP activity in homogenates prepared from this tissue. No difference between ADX and SHAM rats was observed at any age. These results indicate that early adrenalectomy stimulates myelin deposition in the rat brain as part of a more general, long-lasting enhancement of brain growth. Myelin from the brains of ADX animals may be slightly abnormal in its lipid composition. Finally, the optic nerve data may mean that myelination is not affected equally in all areas of the CNS by the loss of adrenal glands.