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

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...

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Published in:International journal of molecular sciences 2022-07, Vol.23 (15), p.8433
Main Authors: Shimizu, Sunao, Kasai, Shuya, Yamazaki, Hiromi, Tatara, Yota, Mimura, Junsei, Engler, Máté János, Tanji, Kunikazu, Nikaido, Yoshikazu, Inoue, Takuro, Suganuma, Hiroyuki, Wakabayashi, Koichi, Itoh, Ken
Format: Article
Language:English
Subjects:
Age
Alzheimer's disease
Animal cognition
Biosynthesis
Broccoli
Clinical trials
Cognitive ability
Cytochrome
Dementia
Deoxyribonucleic acid
DNA
Gene expression
Hippocampus
In vivo methods and tests
Long term memory
Memory
Mitochondria
Mitochondrial DNA
Oral administration
Oxidative stress
Proteins
Respiration
Senescence
Sulforaphane
Transcription factors
Vitamin E
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Summary: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.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms23158433