Sulforaphane Increase Mitochondrial Biogenesis-Related Gene Expression in the Hippocampus and Suppresses Age-Related Cognitive Decline in Mice

Int J Mol Sci. 2022 Jul 29;23(15):8433. doi: 10.3390/ijms23158433.

Abstract

Sulforaphane (SFN) is a potent activator of the transcriptional factor, Nuclear Factor Erythroid 2 (NF-E2)-Related factor 2 (NRF2). SFN and its precursor, glucoraphanin (sulforaphane glucosinolate, SGS), have been shown to ameliorate cognitive function in clinical trials and in vivo studies. However, the effects of SGS on age-related cognitive decline in Senescence-Accelerated Mouse Prone 8 (SAMP8) is unknown. In this study, we determined the preventive potential of SGS on age-related cognitive decline. One-month old SAMP8 mice or control SAM resistance 1 (SAMR1) mice were fed an ad libitum diet with or without SGS-containing broccoli sprout powder (0.3% w/w SGS in diet) until 13 months of age. SGS significantly improved long-term memory in SAMP8 at 12 months of age. Interestingly, SGS increased hippocampal mRNA and protein levels of peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC1α) and mitochondrial transcription factor A (TFAM), which are master regulators of mitochondrial biogenesis, both in SAMR1 and SAMP8 at 13 months of age. Furthermore, mRNAs for nuclear respiratory factor-1 (NRF-1) and mitochondrial DNA-encoded respiratory complex enzymes, but not mitochondrial DNA itself, were increased by SGS in SAMP8 mice. These results suggest that SGS prevents age-related cognitive decline by maintaining mitochondrial function in senescence-accelerated mice.

Keywords: NRF2; PGC1α; TFAM; cognitive decline; glucoraphanin; mitochondrial biogenesis; sulforaphane.

MeSH terms

  • Aging / genetics
  • Aging / metabolism
  • Animals
  • Cognitive Dysfunction* / drug therapy
  • Cognitive Dysfunction* / genetics
  • Cognitive Dysfunction* / metabolism
  • DNA / metabolism
  • Gene Expression
  • Hippocampus / metabolism
  • Isothiocyanates
  • Mice
  • Organelle Biogenesis*
  • Sulfoxides

Substances

  • Isothiocyanates
  • Sulfoxides
  • DNA
  • sulforaphane

Grants and funding

This work was supported by Joint Research Costs for the Department of Vegetable Life Science from Kagome Co., Ltd. (Tokyo, Japan). The funders had no role in study design, data collection, analysis, decision to publish, or preparation of the manuscript. The Kagome Co., Ltd. provided support in the form of salaries for the authors [S.S., T.I. and H.S.] and the research costs as the Joint Research Costs, but did not have any additional roles in the study design, data collection, analysis, decision to publish, or preparation of the manuscript.