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

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.

Sulforaphane Exposure Prevents Cadmium-Induced Toxicity and Mitochondrial Dysfunction in the Nematode Caenorhabditis elegans by Regulating the Insulin/Insulin-like Growth Factor Signaling (IIS) Pathway

“…The beneficial effects on mitochondrial health that we observed suggest that exposure to SFN prevents CdCl 2 -induced mitochondrial dysfunction, and this could be primarily due to the increase in mitochondrial mass. Previous studies have suggested that SFN increases mitochondrial biogenesis in mice with accelerated senescence, which could explain the improvement in ETS activity, restoring ∆Ψm [82]. It has also been demonstrated that SFN enhances multiple mitochondrial bioactivities and bioenergetic parameters such as ∆Ψm, ATP, and ETS by promoting PGC-1α-dependent mitochondrial biogenesis and improving Nrf2-dependent mitochondrial redox regulation in HHL-5 cells and in rats fed a high-fat diet [63].…”

The effect of yttrium oxide nanoparticles on memory, inflammatory responses and mitochondrial biogenesis in cholestatic male Wistar rats

“…One of this study's objectives was to investigate the effects of cholestasis on the expression of genes involved in mitochondrial biogenesis. The ndings demonstrated that cholestasis could impair mitochondrial functions in the hippocampus of rats by reducing the expression of genes involved in mitochondrial biogenesis (Shimizu, et al, 2022).…”

Electroacupuncture treatment ameliorates depressive-like behavior and cognitive dysfunction via CB1R dependent mitochondria biogenesis after experimental global cerebral ischemic stroke

“…Accumulating evidence has suggested a strong correlation between mitochondrial biogenesis and mental disorders and identified the promotion of mitochondrial biogenesis as a promising treatment target for conditions like MDD and anxiety ( Stachowicz et al, 2016 ; Goetzl et al, 2021 ). In the regulation of mitochondrial biogenesis, one of the most studied proteins in signaling pathways are the Nuclear respiratory factor (NRF1) and mitochondrial transcription factor A (TFAM) ( Zhu et al, 2020 ; Shimizu et al, 2022 ). NRF1 is a vital component in controlling the transcription of nuclear-encoded mitochondrial genes, which affect the electron transport chain and induce the protein expression of TFAM.…”