Chronic psychosocial stress and citalopram modulate the expression of the glial proteins GFAP and NDRG2 in the hippocampus

Psychopharmacology (Berl). 2012 Nov;224(1):209-22. doi: 10.1007/s00213-012-2741-x. Epub 2012 May 18.


Rationale: It has been suggested that there are causal relationships between alterations in brain glia and major depression.

Objectives: To investigate whether a depressive-like state induces changes in brain astrocytes, we used chronic social stress in male rats, an established preclinical model of depression. Expression of two astrocytic proteins, the intermediate filament component glial fibrillary acidic protein (GFAP) and the cytoplasmic protein N-myc downregulated gene 2 (NDRG2), was analyzed in the hippocampus. For comparison, expression of the neuronal protein syntaxin-1A was also determined.

Methods: Adult male rats were subjected to daily social defeat for 5 weeks and were concomitantly treated with citalopram (30 mg/kg/day, via the drinking water) for 4 weeks.

Results: Western blot analysis showed that the chronic stress downregulated GFAP but upregulated NDRG2 protein. Citalopram did not prevent these stress effects, but the antidepressant per se downregulated GFAP and upregulated NDRG2 in nonstressed rats. In contrast, citalopram prevented the stress-induced upregulation of the neuronal protein syntaxin-1A.

Conclusions: These data suggest that chronic stress and citalopram differentially affect expression of astrocytic genes while the antidepressant drug does not prevent the stress effects. The inverse regulation of the cytoskeletal protein GFAP and the cytoplasmic protein NDRG2 indicates that the cells undergo profound metabolic changes during stress and citalopram treatment. Furthermore, the present findings indicate that a 4-week treatment with citalopram does not restore normal glial function in the hippocampus, although the behavior of the animals was normalized within this treatment period, as reported previously.

MeSH terms

  • Animals
  • Antidepressive Agents, Second-Generation / pharmacology*
  • Astrocytes / drug effects
  • Astrocytes / metabolism
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology
  • Chronic Disease
  • Citalopram / pharmacology*
  • Depression / drug therapy*
  • Depression / physiopathology
  • Disease Models, Animal
  • Dominance-Subordination
  • Down-Regulation / drug effects
  • Down-Regulation / physiology
  • Glial Fibrillary Acidic Protein / genetics
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Male
  • Nerve Tissue Proteins / genetics
  • Rats
  • Rats, Wistar
  • Stress, Psychological / psychology*
  • Syntaxin 1 / genetics
  • Up-Regulation / drug effects
  • Up-Regulation / physiology


  • Antidepressive Agents, Second-Generation
  • Glial Fibrillary Acidic Protein
  • Ndrg2 protein, rat
  • Nerve Tissue Proteins
  • Syntaxin 1
  • Citalopram