Prolonged corticosterone treatment of adult rats inhibits the proliferation of oligodendrocyte progenitors present throughout white and gray matter regions of the brain

Abstract

It is well established that glucocorticoids inhibit the proliferation of progenitor cells that occurs in the hippocampal dentate gyrus of adult mammals. Active cell proliferation also occurs in the subventricular zone (SVZ) of the lateral ventricle and, to a lesser extent, throughout white and gray matter regions of the adult brain. The aim of the present study was to determine whether extrahippocampal cell proliferation is also affected by glucocorticoids. The cell proliferation marker bromodeoxyuridine (BrdU) was administered to control rats, to adrenalectomized rats, and to rats treated with a daily injection of corticosterone (10 mg/kg) for a period of 15 days. In control and adrenalectomized rats, high to low numerical densities of BrdU‐labeled nuclei were detected within the different forebrain regions examined. In rats treated with corticosterone, a dramatic decrease of cell proliferation was detected in the dentate gyrus, but also throughout all white and gray matter regions examined, except for the SVZ of the lateral ventricle. Double‐labeling experiments indicated that throughout the different white and gray forebrain regions examined, except for the SVZ, BrdU‐labeled nuclei were essentially associated with cells immunostained for the marker of oligodendrocyte progenitors NG2. These data indicate that glucocorticoids inhibit the proliferation of oligodendrocyte precursors located throughout the white and gray matter regions of the adult rat brain. Since the proliferation of oligodendrocyte precursors plays a major role in the processes of remyelination, these data raise the question of possible detrimental effects of therapeutic treatments of CNS trauma based on the administration of glucocorticoids. GLIA 31:219–231, 2000. © 2000 Wiley‐Liss, Inc.

Epigenetic impacts of stress priming of the neuroinflammatory response to sarin surrogate in mice: a model of Gulf War illness

“…As we would not expect neurogenesis to occur in the frontal cortex, this suggests that the increase in the proportion of neurons is driven by a decrease in the absolute number of myelinating oligodendrocytes. A reduced number of oligodendrocytes would be in line with previous work in rats where CORT was shown to reduce the proliferation of oligodendrocytes [ 78 , 79 ]. We emphasize that these are estimated cell proportions; however, the results indicate that stereology to confirm this will be important in future studies.…”

“…Finally, we see evidence of not just a change in gene activity but of a suggested change in cell proportions. This is in line with previous work with CORT [ 78 , 79 ].…”

Epigenetic impacts of stress priming of the neuroinflammatory response to sarin surrogate in mice: a model of Gulf War illness

“…As we would not expect neurogenesis to occur in the frontal cortex, this suggests that the increase in the proportion of neurons is driven by a decrease in the absolute number of myelinating oligodendrocytes. A reduced number of oligodendrocytes would be in line with previous work in rats where CORT was shown to reduce the proliferation of oligodendrocytes [ 78 , 79 ]. We emphasize that these are estimated cell proportions; however, the results indicate that stereology to confirm this will be important in future studies.…”

“…Finally, we see evidence of not just a change in gene activity but of a suggested change in cell proportions. This is in line with previous work with CORT [ 78 , 79 ].…”

Oligodendrocyte involvement in Gulf War Illness

“…In terms of oligodendrocyte and white matter biology, we find that Cort alone has robust protective effects by promoting maturation of oligodendrocytes and decreasing proliferation. These findings are consistent with previous literature exploring the effects of Cort on oligodendrocyte biology (Alonso, ; Miyata et al, ).…”

Effects of progesterone derivatives, dihydroprogesterone and tetrahydroprogesterone, on the subependymal layer of the adult rat

“…By contrast to P metabolites, cell proliferation in the anterior SEL is not changed in the P-treated animals. This result is in agreement with recent studies showing no clear modification of BrdU immunostaining in the SEL after subcutaneous or intraventricular injections of P (Alonso, 2000;Shingo et al, 2003). This different behavior on SEL proliferation can be explained considering the distribution and types of receptors of P, DHP, and THP, and the enzymatic complex regulating their reciprocal interconversion.…”

Epigenetic impacts of stress priming of the neuroinflammatory response to sarin surrogate in mice: a model of Gulf War illness

“…As we would not expect neurogenesis to occur in the frontal cortex, this suggests that the increase in the proportion of neurons is driven by a decrease in the absolute number of myelinating oligodendrocytes. A reduced number of oligodendrocytes would be in line with previous work in rats where CORT was shown to reduce the proliferation of oligodendrocytes [ 78 , 79 ]. We emphasize that these are estimated cell proportions; however, the results indicate that stereology to confirm this will be important in future studies.…”

“…Finally, we see evidence of not just a change in gene activity but of a suggested change in cell proportions. This is in line with previous work with CORT [ 78 , 79 ].…”

Oligodendrocyte involvement in Gulf War Illness

“…In terms of oligodendrocyte and white matter biology, we find that Cort alone has robust protective effects by promoting maturation of oligodendrocytes and decreasing proliferation. These findings are consistent with previous literature exploring the effects of Cort on oligodendrocyte biology (Alonso, ; Miyata et al, ).…”

Effects of progesterone derivatives, dihydroprogesterone and tetrahydroprogesterone, on the subependymal layer of the adult rat

“…By contrast to P metabolites, cell proliferation in the anterior SEL is not changed in the P-treated animals. This result is in agreement with recent studies showing no clear modification of BrdU immunostaining in the SEL after subcutaneous or intraventricular injections of P (Alonso, 2000;Shingo et al, 2003). This different behavior on SEL proliferation can be explained considering the distribution and types of receptors of P, DHP, and THP, and the enzymatic complex regulating their reciprocal interconversion.…”

Epigenetic impacts of stress priming of the neuroinflammatory response to sarin surrogate in mice: a model of Gulf War illness

“…As we would not expect neurogenesis to occur in the frontal cortex, this suggests that the increase in the proportion of neurons is driven by a decrease in the absolute number of myelinating oligodendrocytes. A reduced number of oligodendrocytes would be in line with previous work in rats where CORT was shown to reduce the proliferation of oligodendrocytes [ 78 , 79 ]. We emphasize that these are estimated cell proportions; however, the results indicate that stereology to confirm this will be important in future studies.…”

“…Finally, we see evidence of not just a change in gene activity but of a suggested change in cell proportions. This is in line with previous work with CORT [ 78 , 79 ].…”

Oligodendrocyte involvement in Gulf War Illness

“…In terms of oligodendrocyte and white matter biology, we find that Cort alone has robust protective effects by promoting maturation of oligodendrocytes and decreasing proliferation. These findings are consistent with previous literature exploring the effects of Cort on oligodendrocyte biology (Alonso, ; Miyata et al, ).…”

Effects of progesterone derivatives, dihydroprogesterone and tetrahydroprogesterone, on the subependymal layer of the adult rat

“…By contrast to P metabolites, cell proliferation in the anterior SEL is not changed in the P-treated animals. This result is in agreement with recent studies showing no clear modification of BrdU immunostaining in the SEL after subcutaneous or intraventricular injections of P (Alonso, 2000;Shingo et al, 2003). This different behavior on SEL proliferation can be explained considering the distribution and types of receptors of P, DHP, and THP, and the enzymatic complex regulating their reciprocal interconversion.…”