Effects of Treadmill Exercise on the Expression Level of BAX, BAD, BCL-2, BCL-XL, TFAM, and PGC-1α in the Hippocampus of Thimerosal-Treated Rats

Neurotox Res. 2021 Aug;39(4):1274-1284. doi: 10.1007/s12640-021-00370-w. Epub 2021 May 3.

Abstract

Thimerosal (THIM) induces neurotoxic changes including neuronal death and releases apoptosis inducing factors from mitochondria to cytosol. THIM alters the expression level of factors involved in apoptosis. On the other hand, the anti-apoptotic effects of exercise have been reported. In this study, we aimed to discover the effect of three protocols of treadmill exercise on the expression level of mitochondrial transcription factor A (TFAM), peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), BCL-2-associated death (BAD), BCL-2-associated X (BAX), BCL-XL, and BCL-2 (a pro-survival BCL-2 protein) in the hippocampus of control and THIM-exposed rats. Male Wistar rats were used in this research. Real-time PCR was applied to assess genes expression. The results showed that THIM increased the expression of pro-apoptotic factors (BAD and BAX), decreased the expression of anti-apoptotic factors (BCL-2 and BCL-XL), and decreased the expression of factors involved in mitochondrial biogenesis (TFAM and PGC-1α). Treadmill exercise protocols reversed the effect of THIM on all genes. In addition, treadmill exercise protocols decreased the expression of BAD and BAX, increased the expression of BCL-2, and increased the expression of TFAM and PGC-1α in control rats. In conclusion, THIM induced a pro-apoptotic effect and disturbed mitochondrial biogenesis and stability, whereas treadmill exercise reversed these effects.

Keywords: Apoptosis; Mitochondrial biogenesis; Thimerosal (THIM); Treadmill exercise.

MeSH terms

  • Animals
  • Exercise Test / methods*
  • Gene Expression
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Male
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / biosynthesis
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / genetics
  • Physical Conditioning, Animal / methods
  • Physical Conditioning, Animal / physiology*
  • Preservatives, Pharmaceutical / toxicity
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Rats
  • Rats, Wistar
  • Thimerosal / toxicity*
  • Transcription Factors / biosynthesis
  • Transcription Factors / genetics
  • bcl-2-Associated X Protein / biosynthesis
  • bcl-2-Associated X Protein / genetics
  • bcl-Associated Death Protein / biosynthesis
  • bcl-Associated Death Protein / genetics
  • bcl-X Protein / biosynthesis
  • bcl-X Protein / genetics

Substances

  • Bad protein, rat
  • Bax protein, rat
  • Bcl2l1 protein, rat
  • Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
  • Ppargc1a protein, rat
  • Preservatives, Pharmaceutical
  • Proto-Oncogene Proteins c-bcl-2
  • Tfam protein, rat
  • Transcription Factors
  • bcl-2-Associated X Protein
  • bcl-Associated Death Protein
  • bcl-X Protein
  • Thimerosal