Popular Herb Shows Promise for Counteracting Age-Related Memory Problems

The gut is in a complicated relationship with the brain. The dynamic goes both ways: A troubled gastrointestinal system sends distress signals to the brain, and a bothered brain sends similar signals to the gut. On Monday, at the 2019 Experimental Biology meeting in Orlando, scientists gave a glimpse of what happens to the brain when gut health declines — and presented a delicious intervention that may help prevent that decline from happening.

With the results of a mouse study, scientists from the University of Louisville make a compelling case for the consumption of garlic. This pungent member of the onion genus Allium contains a compound called allyl sulfide, which, as these scientists discovered, helps keep gut microorganisms healthy — which in turn keeps cognitive health robust.

Garlic, they find, may be especially important for the elderly. In older people, the diversity of gut microbiota — the trillions of microorganisms that colonize the gut — is diminished, and this may underlie many ailments of the elderly. As people get older, neurodegenerative diseases like Alzheimer’s and Parkinson’s develop, and in turn, memory and cognitive abilities decline. The scientists suspected changes in the diversity of the gut microbiota could be linked to these deteriorations, and that garlic may help prevent them from happening in the first place.

Lead author Jyotirmaya Behera, Ph.D., said that “dietary administration of garlic containing allyl sulfide” could keep these declines at bay.

The Power of Garlic

The power of garlic was revealed by groups of mice that received an oral supplement of allyl sulfide. The mice that took the supplement were 24 months old (equivalent to 56-69 human years); the other groups were made up of mice that were either 24 months old, or four months old, neither of which received the supplement.

The older mice who received the garlic compound demonstrated better long- and short-term memory than the other 24-month-old mice who did not receive it, the team reports. Notably, they also had healthier gut microbiota. The allyl sulfide supplements appeared to prevent intestinal inflammation.

Furthermore, those mice had higher levels of a protein-coding gene called NDNF. Previously, University of Louisville researchers discovered that this protein is required for long-term and short-term memory consolidation. Now, the scientists suspect that oral allyl sulfide benefits NDNF, in turn stalling cognitive decline. 

At least in mice, allyl sulfide appears to pack a one-two punch that keeps down gastrointestinal inflammation while improving the diversity and maintaining the homeostasis of gut microbiota. And a happy gut means a happy human. The microbial communities that live in us play a fundamental role in our health, the extent of which we’re still discovering.

Abstract:

Advancing age is the top risk factor for the development of neurodegenerative disorders such as Alzheimer’s Disease (AD). However, the contribution of the aging process to Alzheimer’s disease (AD) pathology remain unclear. It is also unclear, whether age-related disruption of the gut-barrier integrity or dysbiosis causes impaired hippocampal memory. Allyl sulfide (AS), an organic sulfur compound in garlic, has many health benefits and is known for its detoxifying agents. However, the precise role of allyl sulfide in regulating hippocampal memory function at mechanistic levels in mice still needs to be investigated. Here we show that memory disturbances with altered hippocampal chromatin plasticity in the aging brain of the mouse are associated with gut-microbiota changes and intragastric administration of allyl sulfide retards age-related defects. To test the hypothesis, we employed 4-months age-matched male wild-type C57BJ/L6 (WT) mice as control group (Young), 24-months old age-matched male WT mice group as aging group (AG) and another 24-months old age-matched male WT mice group received daily AS at the dosage of 2mg/kg/b.wt through oral gavage (AG+AS). The results show that Young and AG+AS mice showed higher behavioral proficiency and more robust long-term and short-term memory compared to AG mice. Gut microbiota is significantly altered as assessed by the denaturing gradient gel electrophoresis (DGGE) analysis in AG group in compared with Young and AG+AS group. The mechanistic study shows that AG mice display an increased plasma level of circulating non-coding RNA-Hotair (lncRNA-Hotair), as assessed by RT2 lncRNA qPCR Assay. To test whether memory impairment correlates with altered hippocampal chromatin plasticity in a lncRNA-Hotair dependent manner, we first investigated the hippocampal histone acetylation pattern in the AG group. The data suggest that lncRNA-Hotair causes a specific deregulation of histone H3 lysine 27 (H3K27) acetylation (ac) at the neuronal derived natriuretic factor (NDNF) promoter of hippocampal tissue of AG group and, therefore, fail to initiate a hippocampal gene transcription associated with memory consolidation. However, administration of AS in the AG group could ameliorate gut dysbiosis and memory functions. In lncRNA-Hotair-deficient mice, which are protected from age-related microbiota changes and memory impairment. Furthermore, restoration of NDNF using recombinant NDNF-therapy reinstates to the recovery of cognitive abilities. In conclusion, our data suggest that lncRNA-Hotair upregulation and H3K27ac regulatory activity may represent an early biomarker in the aging mouse brain. In addition, AS could serve as potential anti-aging therapeutics in treating aging individuals.