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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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The morphology of (a) a BrdU/DCX double positive cell, (b) a BrdU/NeuN double positive cell, (c) a BrdU/GFAP double positive cell. (d) Design of experiment 1. (e) The percentage of phenotypes of BrdU-labeled cells at day 7. Corticosterone treatment significantly reduced the percentage of BrdU cells positive for the immature neuronal marker DCX at this time-point (§F1,11=6.40, P<0.03). (f) The phenotype of BrdU-labeled cells at day 28. Corticosterone treatment significantly reduced the percentage of BrdU cell positive for the mature neuronal marker NeuN at day 28 (§F1,11=31.9, P<0.0001). (g) The phenotype of BrdU-labeled cells at day 28. Corticosterone did not affect the proportion of BrdU cells expressing DCX at day 28. (h) The number of new neurons produced at day 28 calculated using the equation described in Experimental Procedures (data in Table 1). Corticosterone treatment significantly reduced the number of new neurons produced in the dentate gyrus 28 days after BrdU labeling (§F1,11=14.4, P<0.004).
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fig1: The morphology of (a) a BrdU/DCX double positive cell, (b) a BrdU/NeuN double positive cell, (c) a BrdU/GFAP double positive cell. (d) Design of experiment 1. (e) The percentage of phenotypes of BrdU-labeled cells at day 7. Corticosterone treatment significantly reduced the percentage of BrdU cells positive for the immature neuronal marker DCX at this time-point (§F1,11=6.40, P<0.03). (f) The phenotype of BrdU-labeled cells at day 28. Corticosterone treatment significantly reduced the percentage of BrdU cell positive for the mature neuronal marker NeuN at day 28 (§F1,11=31.9, P<0.0001). (g) The phenotype of BrdU-labeled cells at day 28. Corticosterone did not affect the proportion of BrdU cells expressing DCX at day 28. (h) The number of new neurons produced at day 28 calculated using the equation described in Experimental Procedures (data in Table 1). Corticosterone treatment significantly reduced the number of new neurons produced in the dentate gyrus 28 days after BrdU labeling (§F1,11=14.4, P<0.004).

Mentions: Thirty animals, given a single injection of BrdU, were divided into three groups. Group 1 (n=6) was killed 24 h after the BrdU injection. Group 2 (n=12) received a daily injection of peanut oil, beginning 24 h after BrdU. Group 3 (n=12) received 40mg/kg/day corticosterone suspended in peanut oil. Animals (n=6) from each treatment group (2 and 3) were sampled at seven and 28 days after BrdU (Fig. 1d).


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

Wong EY, Herbert J - Neuroscience (2005)

The morphology of (a) a BrdU/DCX double positive cell, (b) a BrdU/NeuN double positive cell, (c) a BrdU/GFAP double positive cell. (d) Design of experiment 1. (e) The percentage of phenotypes of BrdU-labeled cells at day 7. Corticosterone treatment significantly reduced the percentage of BrdU cells positive for the immature neuronal marker DCX at this time-point (§F1,11=6.40, P<0.03). (f) The phenotype of BrdU-labeled cells at day 28. Corticosterone treatment significantly reduced the percentage of BrdU cell positive for the mature neuronal marker NeuN at day 28 (§F1,11=31.9, P<0.0001). (g) The phenotype of BrdU-labeled cells at day 28. Corticosterone did not affect the proportion of BrdU cells expressing DCX at day 28. (h) The number of new neurons produced at day 28 calculated using the equation described in Experimental Procedures (data in Table 1). Corticosterone treatment significantly reduced the number of new neurons produced in the dentate gyrus 28 days after BrdU labeling (§F1,11=14.4, P<0.004).
© Copyright Policy - CC BY
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2651634&req=5

fig1: The morphology of (a) a BrdU/DCX double positive cell, (b) a BrdU/NeuN double positive cell, (c) a BrdU/GFAP double positive cell. (d) Design of experiment 1. (e) The percentage of phenotypes of BrdU-labeled cells at day 7. Corticosterone treatment significantly reduced the percentage of BrdU cells positive for the immature neuronal marker DCX at this time-point (§F1,11=6.40, P<0.03). (f) The phenotype of BrdU-labeled cells at day 28. Corticosterone treatment significantly reduced the percentage of BrdU cell positive for the mature neuronal marker NeuN at day 28 (§F1,11=31.9, P<0.0001). (g) The phenotype of BrdU-labeled cells at day 28. Corticosterone did not affect the proportion of BrdU cells expressing DCX at day 28. (h) The number of new neurons produced at day 28 calculated using the equation described in Experimental Procedures (data in Table 1). Corticosterone treatment significantly reduced the number of new neurons produced in the dentate gyrus 28 days after BrdU labeling (§F1,11=14.4, P<0.004).
Mentions: Thirty animals, given a single injection of BrdU, were divided into three groups. Group 1 (n=6) was killed 24 h after the BrdU injection. Group 2 (n=12) received a daily injection of peanut oil, beginning 24 h after BrdU. Group 3 (n=12) received 40mg/kg/day corticosterone suspended in peanut oil. Animals (n=6) from each treatment group (2 and 3) were sampled at seven and 28 days after BrdU (Fig. 1d).

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