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Role of forebrain and brainstem gluc...

Vincent, Melanie.

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Role of forebrain and brainstem glucocorticoid receptors in dysphoria and hypothalamic-pituitary-adrenal axis.

Record Type:	Electronic resources : Monograph/item
Title/Author:	Role of forebrain and brainstem glucocorticoid receptors in dysphoria and hypothalamic-pituitary-adrenal axis./
Author:	Vincent, Melanie.
Published:	Ann Arbor : ProQuest Dissertations & Theses, : 2014,
Description:	162 p.
Notes:	Source: Dissertation Abstracts International, Volume: 75-05(E), Section: B.
Contained By:	Dissertation Abstracts International75-05B(E).
Subject:	Neurosciences. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3579042
ISBN:	9781303755231

Role of forebrain and brainstem glucocorticoid receptors in dysphoria and hypothalamic-pituitary-adrenal axis.
Vincent, Melanie.

Role of forebrain and brainstem glucocorticoid receptors in dysphoria and hypothalamic-pituitary-adrenal axis. - Ann Arbor : ProQuest Dissertations & Theses, 2014 - 162 p.

Source: Dissertation Abstracts International, Volume: 75-05(E), Section: B.

Thesis (Ph.D.)--Albany Medical College of Union University, 2014.

Abnormal hypothalamic-pituitary-adrenal (HPA) activity is observed in depression and anxiety (dysphoria) disorders. There is evidence that glucocorticoids released by the HPA axis may not only reflect but also contribute to dysphoria symptoms. Antidepressants also alter GR expression and HPA activity; however, it remains unclear if these changes facilitate the mood-elevating effects of antidepressant drugs. Since the location of GR mediating dysphoria and antidepressant action remains unclear, we used two mouse models to determine the role of forebrain GR and non-forebrain GR in dysphoria behavior and HPA activity. Forebrain GR deletion (FBGRKO-T50 mice) reportedly produces a depression-like phenotype of despair-like behavior and HPA hyperactivity. We tested if forebrain GR deletion would reduce behavioral sensitivity to glucocorticoids and antidepressants in mice with forebrain deletion on a C57BL6 background (FBGRKO-T29-1 mice). FBGRKO-T29-1 mice did not show the previously reported depression-like phenotype, but were still sensitive to the depressive-like effects of glucocorticoids and responded to different classes of acute antidepressant treatment. Our results suggest that GR expressed outside of the targeted forebrain regions mediate depression-like behavior and antidepressant response. Therefore, we virally-transduced GR deletion in the DRN, a non-forebrain region, using pseudotype adeno-associated virus. Since our lab has shown that antidepressants decrease DRN GR and increase gene expression of tryptophan hydroxylase 2 (TPH2), the rate-limiting enzyme for serotonin synthesis, we hypothesized that deleting DRN GR would reduce dysphoria-like behavior and increase TPH2 expression. We also hypothesized that DRN GR deletion would disinhibit HPA activity. DRN GR did not affect TPH2 gene expression, but did, consistent with our hypothesis, have anxiolytic- and antidepressant-like effects on behavior and impaired HPA negative feedback during stress. Taken together, our results indicate that GR located outside of the forebrain, such as DRN GR, can mediate dysphoria-like behavior and HPA activity.

ISBN: 9781303755231Subjects--Topical Terms:

588700
Neurosciences.

Role of forebrain and brainstem glucocorticoid receptors in dysphoria and hypothalamic-pituitary-adrenal axis.
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500 $a Source: Dissertation Abstracts International, Volume: 75-05(E), Section: B.
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502 $a Thesis (Ph.D.)--Albany Medical College of Union University, 2014.
520 $a Abnormal hypothalamic-pituitary-adrenal (HPA) activity is observed in depression and anxiety (dysphoria) disorders. There is evidence that glucocorticoids released by the HPA axis may not only reflect but also contribute to dysphoria symptoms. Antidepressants also alter GR expression and HPA activity; however, it remains unclear if these changes facilitate the mood-elevating effects of antidepressant drugs. Since the location of GR mediating dysphoria and antidepressant action remains unclear, we used two mouse models to determine the role of forebrain GR and non-forebrain GR in dysphoria behavior and HPA activity. Forebrain GR deletion (FBGRKO-T50 mice) reportedly produces a depression-like phenotype of despair-like behavior and HPA hyperactivity. We tested if forebrain GR deletion would reduce behavioral sensitivity to glucocorticoids and antidepressants in mice with forebrain deletion on a C57BL6 background (FBGRKO-T29-1 mice). FBGRKO-T29-1 mice did not show the previously reported depression-like phenotype, but were still sensitive to the depressive-like effects of glucocorticoids and responded to different classes of acute antidepressant treatment. Our results suggest that GR expressed outside of the targeted forebrain regions mediate depression-like behavior and antidepressant response. Therefore, we virally-transduced GR deletion in the DRN, a non-forebrain region, using pseudotype adeno-associated virus. Since our lab has shown that antidepressants decrease DRN GR and increase gene expression of tryptophan hydroxylase 2 (TPH2), the rate-limiting enzyme for serotonin synthesis, we hypothesized that deleting DRN GR would reduce dysphoria-like behavior and increase TPH2 expression. We also hypothesized that DRN GR deletion would disinhibit HPA activity. DRN GR did not affect TPH2 gene expression, but did, consistent with our hypothesis, have anxiolytic- and antidepressant-like effects on behavior and impaired HPA negative feedback during stress. Taken together, our results indicate that GR located outside of the forebrain, such as DRN GR, can mediate dysphoria-like behavior and HPA activity.
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