Carnosic acid ameliorates depressive-like symptoms along with the modulation of FGF9 in the hippocampus of middle carotid artery occlusion-induced Sprague Dawley rats

Phytother Res. 2021 Jan;35(1):384-391. doi: 10.1002/ptr.6810. Epub 2020 Aug 11.

Abstract

The increased survival rate of stroke patients has led to the higher incidences of post-stroke depression. Carnosic acid has the ability to cross blood brain barrier with good neuro-modulatory actions. Recently, inclined level of fibroblast growth factor 9 (FGF9) in the postmortem brain of the depressed patients was noted. Therefore, in the present study, the effect of carnosic acid on post-stroke depression-like behavior, and the expression of FGF9 were evaluated. After 3 weeks of middle carotid artery occlusion in Sprague Dawley rats, carnosic acid (20 and 40 mg/kg) was administered for 2 weeks. Sucrose preference test, forced swimming test, and open field test were performed and hippocampi were analyzed for FGF9 and FGFR-3. In comparison to post-stroke depressed rats, carnosic acid increased the sucrose preference, and reduced the immobility time of the rats by ~2×. The speed and distance-covered were also increased. At 40 mg/kg, FGF9 was reduced by ~3× while FGFR-3/Actin was increased by ~1.5×. Altogether results suggest anti-depressant-like activity of carnosic acid in post-stroke depressed rats with decreased expression of hippocampal FGF9.

Keywords: FGF9; FGFR-3; carnosic acid; post-stroke depression; sucrose preference.

MeSH terms

  • Abietanes / therapeutic use*
  • Animals
  • Brain / metabolism
  • Brain / physiopathology
  • Carotid Arteries / pathology
  • Depression / drug therapy*
  • Depression / etiology
  • Disease Models, Animal
  • Fibroblast Growth Factor 9 / metabolism*
  • Hippocampus / drug effects*
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, Fibroblast Growth Factor, Type 3 / metabolism
  • Stroke / complications
  • Stroke / physiopathology*
  • Swimming

Substances

  • Abietanes
  • Fgf9 protein, rat
  • Fibroblast Growth Factor 9
  • Fgfr3 protein, rat
  • Receptor, Fibroblast Growth Factor, Type 3
  • salvin