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: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Psychological and Brain Sciences, Johns Hopkins University, Baltimore, MD 21218, USA. astrana1@jhu.edu
authors.forename: Alexis M
authors.initials: AM
authors.lastname: Stranahan
authors.forename: Thiruma V
authors.initials: TV
authors.lastname: Arumugam
authors.forename: Mark P
authors.initials: MP
authors.lastname: Mattson
mesh_terms: D000315:Adrenalectomy / Q000009:adverse effects; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D003345:Corticosterone / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism*; D004435:Eating / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009414:Nerve Growth Factors / Q000378:metabolism; D020813:Receptor, trkB / Q000378:metabolism*; D054411:Receptors, Leptin / Q000235:genetics*; D015430:Weight Gain / Q000187:drug effects / Q000235:genetics
chemical_list: D001786:Blood Glucose; D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D054411:Receptors, Leptin; C518911:neurotropin 3, mouse; D020813:Receptor, trkB; D003345:Corticosterone