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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 showing the corticoid manipulations in the different groups of animals. (b, c) There was no observable effect by ADX on differentiation of the newly-formed cells as detected by DCX, NeuN and GFAP at day 7 and day 28. (d) Combining the survival data (Table 1) revealed that ADX significantly increased the number of new neurons formed in the dentate gyrus 28 days after BrdU labeling (§P<0.025).
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fig4: (a) Diagram showing the corticoid manipulations in the different groups of animals. (b, c) There was no observable effect by ADX on differentiation of the newly-formed cells as detected by DCX, NeuN and GFAP at day 7 and day 28. (d) Combining the survival data (Table 1) revealed that ADX significantly increased the number of new neurons formed in the dentate gyrus 28 days after BrdU labeling (§P<0.025).

Mentions: Four groups of animals were used in this experiment (n=56). They all received a single injection of BrdU (200mg/kg, i.p.) to label the new-born cells. In group 1 (n=8), animals were killed 24 h after BrdU labeling, whereas in group 2 (n=16) they were sham-operated 24 h after BrdU and implanted s.c. with a cholesterol pellet. Eight rats were perfused at seven and 28 days after surgery. Group 3 (n=16) was bilaterally ADX 24 h after BrdU and implanted with a cholesterol pellet. Rats (n=8) were sampled at the same intervals. Group four (n=16) were also ADX, but received a 50% corticosterone pellet (200–250 mg). They were sampled at the same intervals (Fig. 4a).


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

Wong EY, Herbert J - Neuroscience (2005)

(a) Diagram showing the corticoid manipulations in the different groups of animals. (b, c) There was no observable effect by ADX on differentiation of the newly-formed cells as detected by DCX, NeuN and GFAP at day 7 and day 28. (d) Combining the survival data (Table 1) revealed that ADX significantly increased the number of new neurons formed in the dentate gyrus 28 days after BrdU labeling (§P<0.025).
© Copyright Policy - CC BY
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2651634&req=5

fig4: (a) Diagram showing the corticoid manipulations in the different groups of animals. (b, c) There was no observable effect by ADX on differentiation of the newly-formed cells as detected by DCX, NeuN and GFAP at day 7 and day 28. (d) Combining the survival data (Table 1) revealed that ADX significantly increased the number of new neurons formed in the dentate gyrus 28 days after BrdU labeling (§P<0.025).
Mentions: Four groups of animals were used in this experiment (n=56). They all received a single injection of BrdU (200mg/kg, i.p.) to label the new-born cells. In group 1 (n=8), animals were killed 24 h after BrdU labeling, whereas in group 2 (n=16) they were sham-operated 24 h after BrdU and implanted s.c. with a cholesterol pellet. Eight rats were perfused at seven and 28 days after surgery. Group 3 (n=16) was bilaterally ADX 24 h after BrdU and implanted with a cholesterol pellet. Rats (n=8) were sampled at the same intervals. Group four (n=16) were also ADX, but received a 50% corticosterone pellet (200–250 mg). They were sampled at the same intervals (Fig. 4a).

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