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

Stranahan, Alexis M., Arumugam, Thiruma V. and Mattson, Mark P. (2011) 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. Neuroendocrinology, 93 1: 58-64. doi:10.1159/000322808


Author Stranahan, Alexis M.
Arumugam, Thiruma V.
Mattson, Mark P.
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
Journal name Neuroendocrinology   Check publisher's open access policy
ISSN 0028-3835
1423-0194
Publication date 2011
Year available 2010
Sub-type Article (original research)
DOI 10.1159/000322808
Volume 93
Issue 1
Start page 58
End page 64
Total pages 7
Place of publication Basel, Switzerland
Publisher Karger
Collection year 2012
Language eng
Formatted 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. Copyright © 2010 S. Karger AG, Basel.
Keyword Diabetes
Glucocorticoid
Neurotropic factor
Hippocampus
Hypothalamus
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status Non-UQ
Additional Notes Published online:13 December 2010.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
School of Biomedical Sciences Publications
 
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Created: Mon, 14 Feb 2011, 20:55:20 EST by Dr Thiruma V Arumugam on behalf of School of Biomedical Sciences