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Raised circulating corticosterone inhibits neuronal differentiation of progenitor cells in the adult hippocampus.

Wong EY, Herbert J - Neuroscience (2005)

Bottom Line: Similar to its effect on survival, post-mitotic corticosterone also regulates neuronal differentiation in a time-dependent fashion, but this action is most prominent from around 19-27 days after the cells were born.Combining these data with previous survival data obtained from the same animals allowed us to estimate the total number of neurons formed resulting from different corticoid treatments.Raised corticosterone significantly reduced neuronal production while adrenalectomy resulted in significantly higher number of neurons in the adult male rat hippocampus.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.

ABSTRACT
Neurons are added throughout life to the dentate gyrus of the hippocampus of the mammalian brain. Progenitors residing in the dentate gyrus progress through three distinct stages of adult neurogenesis: proliferation, survival and differentiation. One of the most potent factors which regulates adult neurogenesis is adrenal-derived glucocorticoids. Raised levels of glucocorticoids suppress progenitor division, while removal of glucocorticoids by adrenalectomy stimulates proliferation of these cells in the dentate gyrus. We have recently reported that both pre- and post-mitotic corticoid environments powerfully regulate survival of progenitor cells in a time-dependent manner. However, it is unknown if glucocorticoids alter the process of neuronal differentiation, since not all of the newly-formed cells acquire a neuronal fate during development. Here we employ triple immuno-fluorescence staining techniques to phenotype surviving progenitor cells 28 days after labeling. Results show that high levels of corticosterone (the major glucocorticoid in rodents) either before or after progenitor labeling discouraged the acquisition of neuronal fate. Similar to its effect on survival, post-mitotic corticosterone also regulates neuronal differentiation in a time-dependent fashion, but this action is most prominent from around 19-27 days after the cells were born. In contrast, a corticoid-free environment either before or after progenitor proliferation did not affect neuronal differentiation. Combining these data with previous survival data obtained from the same animals allowed us to estimate the total number of neurons formed resulting from different corticoid treatments. Raised corticosterone significantly reduced neuronal production while adrenalectomy resulted in significantly higher number of neurons in the adult male rat hippocampus.

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(a) Diagram depicting phased (9 days) corticosterone treatment for the seven groups over 27 days. (b) Corticosterone during period 3 significantly reduced neuronal differentiation (†F1,15=6.8, P<0.02), but not 1 or 2 alone. Giving corticosterone for 18 days or more significantly reduced proliferation (1+2+3: §F1,15=44.3, P<0.0001; 1+2: ‡F1,15=9.62, P<0.008; 2+3: ΨF1,15=12.4, P<0.008). (c) Corticosterone treatment for 18 days or more (1+2 or 2+3 or 1+2+3) significantly reduced the numbers of new neurons 27 days after BrdU labeling (1+2: †P<0.001; 2+3: ‡P<0.002; 1+2+3: §P<0.0001).
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fig2: (a) Diagram depicting phased (9 days) corticosterone treatment for the seven groups over 27 days. (b) Corticosterone during period 3 significantly reduced neuronal differentiation (†F1,15=6.8, P<0.02), but not 1 or 2 alone. Giving corticosterone for 18 days or more significantly reduced proliferation (1+2+3: §F1,15=44.3, P<0.0001; 1+2: ‡F1,15=9.62, P<0.008; 2+3: ΨF1,15=12.4, P<0.008). (c) Corticosterone treatment for 18 days or more (1+2 or 2+3 or 1+2+3) significantly reduced the numbers of new neurons 27 days after BrdU labeling (1+2: †P<0.001; 2+3: ‡P<0.002; 1+2+3: §P<0.0001).

Mentions: Fifty-six intact rats were given BrdU as above, and then received various regimens of daily s.c. injections of either corticosterone (40mg/kg/day) or oil for 27 days. They were divided into seven groups of eight rats each. Group 1 received oil throughout. The next three groups received corticosterone for 9 days each, or oil otherwise. The start of corticosterone was staggered by nine days in each group (group two days 1–9, group three days 10–18, group four days 19–27). Group five received CORT on days 1–18, group six days 10–27, and group seven days 1–27. All rats were killed on day 28 (Fig. 2a).


Raised circulating corticosterone inhibits neuronal differentiation of progenitor cells in the adult hippocampus.

Wong EY, Herbert J - Neuroscience (2005)

(a) Diagram depicting phased (9 days) corticosterone treatment for the seven groups over 27 days. (b) Corticosterone during period 3 significantly reduced neuronal differentiation (†F1,15=6.8, P<0.02), but not 1 or 2 alone. Giving corticosterone for 18 days or more significantly reduced proliferation (1+2+3: §F1,15=44.3, P<0.0001; 1+2: ‡F1,15=9.62, P<0.008; 2+3: ΨF1,15=12.4, P<0.008). (c) Corticosterone treatment for 18 days or more (1+2 or 2+3 or 1+2+3) significantly reduced the numbers of new neurons 27 days after BrdU labeling (1+2: †P<0.001; 2+3: ‡P<0.002; 1+2+3: §P<0.0001).
© Copyright Policy - CC BY
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2651634&req=5

fig2: (a) Diagram depicting phased (9 days) corticosterone treatment for the seven groups over 27 days. (b) Corticosterone during period 3 significantly reduced neuronal differentiation (†F1,15=6.8, P<0.02), but not 1 or 2 alone. Giving corticosterone for 18 days or more significantly reduced proliferation (1+2+3: §F1,15=44.3, P<0.0001; 1+2: ‡F1,15=9.62, P<0.008; 2+3: ΨF1,15=12.4, P<0.008). (c) Corticosterone treatment for 18 days or more (1+2 or 2+3 or 1+2+3) significantly reduced the numbers of new neurons 27 days after BrdU labeling (1+2: †P<0.001; 2+3: ‡P<0.002; 1+2+3: §P<0.0001).
Mentions: Fifty-six intact rats were given BrdU as above, and then received various regimens of daily s.c. injections of either corticosterone (40mg/kg/day) or oil for 27 days. They were divided into seven groups of eight rats each. Group 1 received oil throughout. The next three groups received corticosterone for 9 days each, or oil otherwise. The start of corticosterone was staggered by nine days in each group (group two days 1–9, group three days 10–18, group four days 19–27). Group five received CORT on days 1–18, group six days 10–27, and group seven days 1–27. All rats were killed on day 28 (Fig. 2a).

Bottom Line: Similar to its effect on survival, post-mitotic corticosterone also regulates neuronal differentiation in a time-dependent fashion, but this action is most prominent from around 19-27 days after the cells were born.Combining these data with previous survival data obtained from the same animals allowed us to estimate the total number of neurons formed resulting from different corticoid treatments.Raised corticosterone significantly reduced neuronal production while adrenalectomy resulted in significantly higher number of neurons in the adult male rat hippocampus.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy, University of Cambridge, Downing Street, Cambridge CB2 3DY, UK.

ABSTRACT
Neurons are added throughout life to the dentate gyrus of the hippocampus of the mammalian brain. Progenitors residing in the dentate gyrus progress through three distinct stages of adult neurogenesis: proliferation, survival and differentiation. One of the most potent factors which regulates adult neurogenesis is adrenal-derived glucocorticoids. Raised levels of glucocorticoids suppress progenitor division, while removal of glucocorticoids by adrenalectomy stimulates proliferation of these cells in the dentate gyrus. We have recently reported that both pre- and post-mitotic corticoid environments powerfully regulate survival of progenitor cells in a time-dependent manner. However, it is unknown if glucocorticoids alter the process of neuronal differentiation, since not all of the newly-formed cells acquire a neuronal fate during development. Here we employ triple immuno-fluorescence staining techniques to phenotype surviving progenitor cells 28 days after labeling. Results show that high levels of corticosterone (the major glucocorticoid in rodents) either before or after progenitor labeling discouraged the acquisition of neuronal fate. Similar to its effect on survival, post-mitotic corticosterone also regulates neuronal differentiation in a time-dependent fashion, but this action is most prominent from around 19-27 days after the cells were born. In contrast, a corticoid-free environment either before or after progenitor proliferation did not affect neuronal differentiation. Combining these data with previous survival data obtained from the same animals allowed us to estimate the total number of neurons formed resulting from different corticoid treatments. Raised corticosterone significantly reduced neuronal production while adrenalectomy resulted in significantly higher number of neurons in the adult male rat hippocampus.

Show MeSH
Related in: MedlinePlus