Region specific decrease in glial fibrillary acidic protein immunoreactivity in the brain of a rat model of depression

Neuroscience. 2009 Mar 17;159(2):915-25. doi: 10.1016/j.neuroscience.2008.10.018. Epub 2008 Nov 1.

Abstract

A growing body of evidence from human postmortem and animal studies suggests that deficits in glial cell (particularly astrocytes) density and function, in limbic regions of the brain contribute to the etiology of depressive disorders. Despite the widespread use of Wistar-Kyoto (WKY) rat strain as a model of depression and stress susceptibility, there is a paucity of data examining whether alterations in brain astrocytic population are present in the model. In the present study, we investigated the expression of the astrocytic markers glial fibrillary acidic protein (GFAP) in various brain regions in WKY rats in comparison to Sprague-Dawley rats. A significant deficit in GFAP-immunoreactive cells was found in the prefrontal cortex region (infralimbic, prelimbic and anterior cingulate cortex), in the basolateral amygdala as well as in the hippocampus (CA3 and dentate gyrus) in WKY rat brain. No statistical difference was found in the other brain regions analyzed (insular cortex, somatosensory cortex, CA1 and callosal white matter). No difference was found in the total density of astrocytes (assessed by s-100beta immunoreactivity), neurons (determined by NeuN expression) or in the total number of cells in the regions of interest. A slight increase in the intensity of s-100beta immunoreactivity was observed. The lower expression of GFAP in WKY rats was further confirmed by Western-blot analysis. These results suggest that specific astrocytic deficits in GFAP expression in corticolimbic circuits may be a general correlate of depressive-like behavior in animal models in addition to human major depression. Moreover, they suggest that glial physiology may become a therapeutic target in depression and other stress-related conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Brain / pathology*
  • Cell Count / methods
  • Depression / genetics
  • Depression / pathology*
  • Disease Models, Animal
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / physiology*
  • Glial Fibrillary Acidic Protein / metabolism*
  • Male
  • Nerve Growth Factors / metabolism
  • Neuroglia / metabolism
  • Neuroglia / pathology
  • Phosphopyruvate Hydratase / metabolism
  • Rats
  • Rats, Inbred WKY
  • Rats, Sprague-Dawley
  • S100 Calcium Binding Protein beta Subunit
  • S100 Proteins / metabolism

Substances

  • Glial Fibrillary Acidic Protein
  • Nerve Growth Factors
  • S100 Calcium Binding Protein beta Subunit
  • S100 Proteins
  • Phosphopyruvate Hydratase