Lowering corticosterone levels reinstates hippocampal brain-derived neurotropic factor and trkb expression without influencing deficits in hypothalamic brain-derived neurotropic factor expression in leptin receptor-deficient mice

Alexis Michelle Stranahan, Thiruma V. Arumugam, Mark P. Mattson

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Background/Aims: Changes in the glucocorticoid milieu contribute to alterations in neurotropic factor expression across multiple brain regions. Insulin-resistant diabetes is often accompanied by dysregulation of adrenal steroid production in humans and animal models. Leptin receptor-deficient mice (db/db) show reduced expression of brain-derived neurotropic factor (BDNF) in the hippocampus and increases in circulating corticosterone levels, but the extent to which elevated corticosterone levels mediate deficits in BDNF expression has not been determined. Methods: Using in situ hybridization, we measured the expression of BDNF, its receptor TrkB, and neurotropin-3 (NT-3) in the hippocampus and hypothalamus of db/db mice and wild-type controls following adrenalectomy and low-dose corticosterone replacement (ADX+CORT) or sham operation. Results: Lowering corticosterone levels restored BDNF and TrkB expression in the hippocampus of db/db mice. However, deficits in hypothalamic BDNF expression were not reversed following ADX+CORT. There was no effect of genotype or adrenalectomy on NT-3 expression in any brain region examined. Conclusion: Leptin receptor-deficient mice exhibit reduced BDNF expression in the hippocampus and hypothalamus. In the db/db mouse hippocampus, suppression of BDNF occurs in a glucocorticoid-dependent fashion, while hypothalamic BDNF expression is reduced via glucocorticoid-independent mechanisms. Region-specific signals therefore play a role in the interaction between corticosteroids and neurotropic factor expression.

Original languageEnglish (US)
Pages (from-to)58-64
Number of pages7
JournalNeuroendocrinology
Volume93
Issue number1
DOIs
StatePublished - Feb 1 2011

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Corticosterone
Brain
Hippocampus
Glucocorticoids
Adrenalectomy
Hypothalamus
mouse leptin receptor
trkB Receptor
In Situ Hybridization
Adrenal Cortex Hormones
Animal Models
Steroids
Genotype
Insulin

Keywords

  • Diabetes
  • Glucocorticoid
  • Hippocampus
  • Hypothalamus
  • Neurotropic factor

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Endocrine and Autonomic Systems
  • Cellular and Molecular Neuroscience

Cite this

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title = "Lowering corticosterone levels reinstates hippocampal brain-derived neurotropic factor and trkb expression without influencing deficits in hypothalamic brain-derived neurotropic factor expression in leptin receptor-deficient mice",
abstract = "Background/Aims: Changes in the glucocorticoid milieu contribute to alterations in neurotropic factor expression across multiple brain regions. Insulin-resistant diabetes is often accompanied by dysregulation of adrenal steroid production in humans and animal models. Leptin receptor-deficient mice (db/db) show reduced expression of brain-derived neurotropic factor (BDNF) in the hippocampus and increases in circulating corticosterone levels, but the extent to which elevated corticosterone levels mediate deficits in BDNF expression has not been determined. Methods: Using in situ hybridization, we measured the expression of BDNF, its receptor TrkB, and neurotropin-3 (NT-3) in the hippocampus and hypothalamus of db/db mice and wild-type controls following adrenalectomy and low-dose corticosterone replacement (ADX+CORT) or sham operation. Results: Lowering corticosterone levels restored BDNF and TrkB expression in the hippocampus of db/db mice. However, deficits in hypothalamic BDNF expression were not reversed following ADX+CORT. There was no effect of genotype or adrenalectomy on NT-3 expression in any brain region examined. Conclusion: Leptin receptor-deficient mice exhibit reduced BDNF expression in the hippocampus and hypothalamus. In the db/db mouse hippocampus, suppression of BDNF occurs in a glucocorticoid-dependent fashion, while hypothalamic BDNF expression is reduced via glucocorticoid-independent mechanisms. Region-specific signals therefore play a role in the interaction between corticosteroids and neurotropic factor expression.",
keywords = "Diabetes, Glucocorticoid, Hippocampus, Hypothalamus, Neurotropic factor",
author = "Stranahan, {Alexis Michelle} and Arumugam, {Thiruma V.} and Mattson, {Mark P.}",
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AU - Arumugam, Thiruma V.

AU - Mattson, Mark P.

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N2 - Background/Aims: Changes in the glucocorticoid milieu contribute to alterations in neurotropic factor expression across multiple brain regions. Insulin-resistant diabetes is often accompanied by dysregulation of adrenal steroid production in humans and animal models. Leptin receptor-deficient mice (db/db) show reduced expression of brain-derived neurotropic factor (BDNF) in the hippocampus and increases in circulating corticosterone levels, but the extent to which elevated corticosterone levels mediate deficits in BDNF expression has not been determined. Methods: Using in situ hybridization, we measured the expression of BDNF, its receptor TrkB, and neurotropin-3 (NT-3) in the hippocampus and hypothalamus of db/db mice and wild-type controls following adrenalectomy and low-dose corticosterone replacement (ADX+CORT) or sham operation. Results: Lowering corticosterone levels restored BDNF and TrkB expression in the hippocampus of db/db mice. However, deficits in hypothalamic BDNF expression were not reversed following ADX+CORT. There was no effect of genotype or adrenalectomy on NT-3 expression in any brain region examined. Conclusion: Leptin receptor-deficient mice exhibit reduced BDNF expression in the hippocampus and hypothalamus. In the db/db mouse hippocampus, suppression of BDNF occurs in a glucocorticoid-dependent fashion, while hypothalamic BDNF expression is reduced via glucocorticoid-independent mechanisms. Region-specific signals therefore play a role in the interaction between corticosteroids and neurotropic factor expression.

AB - Background/Aims: Changes in the glucocorticoid milieu contribute to alterations in neurotropic factor expression across multiple brain regions. Insulin-resistant diabetes is often accompanied by dysregulation of adrenal steroid production in humans and animal models. Leptin receptor-deficient mice (db/db) show reduced expression of brain-derived neurotropic factor (BDNF) in the hippocampus and increases in circulating corticosterone levels, but the extent to which elevated corticosterone levels mediate deficits in BDNF expression has not been determined. Methods: Using in situ hybridization, we measured the expression of BDNF, its receptor TrkB, and neurotropin-3 (NT-3) in the hippocampus and hypothalamus of db/db mice and wild-type controls following adrenalectomy and low-dose corticosterone replacement (ADX+CORT) or sham operation. Results: Lowering corticosterone levels restored BDNF and TrkB expression in the hippocampus of db/db mice. However, deficits in hypothalamic BDNF expression were not reversed following ADX+CORT. There was no effect of genotype or adrenalectomy on NT-3 expression in any brain region examined. Conclusion: Leptin receptor-deficient mice exhibit reduced BDNF expression in the hippocampus and hypothalamus. In the db/db mouse hippocampus, suppression of BDNF occurs in a glucocorticoid-dependent fashion, while hypothalamic BDNF expression is reduced via glucocorticoid-independent mechanisms. Region-specific signals therefore play a role in the interaction between corticosteroids and neurotropic factor expression.

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