Hippocampal FGF-2 and FGFR1 mRNA expression in major depression, schizophrenia and bipolar disorder

Brain Res Bull. 2006 Jul 31;70(3):221-7. doi: 10.1016/j.brainresbull.2006.04.008. Epub 2006 May 12.

Abstract

Introduction: FGF-2 is important for stem cell proliferation, neocortical development and adult neuronal survival and growth. Reduced frontal cortical FGF-2 expression is described in major depression and is attenuated by antidepressants. We determined the distribution of hippocampal FGF-2 and its receptor (FGFR1) mRNA in post-mortem brains of people who suffered from major depression, bipolar disorder and schizophrenia and those of controls.

Methods: FGF-2 and FGFR1 mRNA were measured within hippocampal CA1, CA4 regions and the dentate gyrus (DG), using in situ hybridization. Within hippocampal regions, cellular staining was compared between diagnostic groups, using repeated measures analysis of variance.

Results: The density of FGF-2 mRNA+ cells in CA4 was reduced in depression compared to controls. The percentage of FGFR1 mRNA+ cells was higher in depression (CA1 and CA4) and schizophrenia (CA4) than in controls. FGFR1 mRNA expression was higher in depression than in the other groups in CA1, CA4 and DG. Overall FGF-2 mRNA expression was higher in DG than in CA1 and CA4.

Conclusions: We found raised measures of FGFR1 mRNA+ in major depression and, less so, in schizophrenia, along with reduced FGF-2 mRNA density in depression. Perturbations of FGF regulation could be relevant to the pathogenesis of both disorders as FGF-2 and FGFR1 are implicated in normal hippocampal synaptology, stem cell recruitment, and connectivity, and are modulated by corticosteroids.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antipsychotic Agents / therapeutic use
  • Bipolar Disorder / drug therapy
  • Bipolar Disorder / metabolism*
  • Clozapine / therapeutic use
  • Depressive Disorder, Major / metabolism*
  • Female
  • Fibroblast Growth Factor 2 / biosynthesis*
  • Fibroblast Growth Factor 2 / drug effects
  • Gene Expression / drug effects
  • Hippocampus / metabolism*
  • Humans
  • Image Processing, Computer-Assisted
  • In Situ Hybridization
  • Male
  • Middle Aged
  • RNA, Messenger / analysis
  • Receptor, Fibroblast Growth Factor, Type 1 / biosynthesis*
  • Receptor, Fibroblast Growth Factor, Type 1 / drug effects
  • Schizophrenia / drug therapy
  • Schizophrenia / metabolism*

Substances

  • Antipsychotic Agents
  • RNA, Messenger
  • Fibroblast Growth Factor 2
  • FGFR1 protein, human
  • Receptor, Fibroblast Growth Factor, Type 1
  • Clozapine