LH dipeptide may improve mental health

Japanese researchers have revealed the effect of the dipeptide leucine–histidine (LH) — found in fermented foods such as blue cheese and natto (fermented soy beans) — in suppressing microglial activation and depression-associated emotional disturbances. Their work has been reported in the journal Nutrients.

Recent studies have shown the role in depression of microglia — immune cells in the central nervous system that are normally responsible for removing waste products but can cause inflammation in the brain when they are activated. Many findings have suggested a link between depression and brain inflammation, and anti-inflammatory drugs have been shown to improve depression symptoms. It has also been reported that consumption of fermented products is associated with reduced depression symptoms. However, the nutritional components that suppress microglia activation and depression are not well understood.

A research group led by Kobe University’s Professor Tomoyuki Furuyashiki and Associate Professor Shiho Kitaoka, in collaboration with researcher Yasuhisa Ano of Kirin Holdings, evaluated the effects of 336 dipeptides on microglia activation, with LH dipeptide discovered to be a potent anti-inflammatory agent. LH dipeptide inhibited the secretion of inflammatory cytokines (signalling molecules such as TNF-α that are secreted from cells to promote inflammation) from microglia.

Further studies were performed on mice to evaluate LH dipeptide’s impact on brain inflammation and emotional disturbances. The LH dipeptide was labelled with radioactive isotopes so that its movement through the body could be tracked; this confirmed that the dipeptide travelled to the brain after oral administration.

To analyse the effect of LH dipeptide on brain inflammation, mice were injected with LPS (a bacterial component that elicits inflammation), which increased the amount of the cytokines TNF-α and IL-1β in the frontal cortex and hippocampus of the brain. Repeated oral administrations with LH dipeptide reduced the amounts of these cytokines in the brain. These results show that LH dipeptide suppressed brain inflammation.

The team then analysed the effect of LH dipeptide on depression-associated emotional disturbances. First, individual mice were exposed to the tail suspension test (TST), where they were suspended by their tails in a box for six minutes. The time that mice are immobile was measured, as this is a behavioural indication of depression. LPS treatment induced brain inflammation and prolonged immobility time in the TST. However, repeated oral administration with LH dipeptide was shown to prevent this pro-depressive effect of LPS.

Second, mice were confronted with repeated social defeat stress (R-SDS). This involved putting each of the test mice in cages with an aggressive mouse for 10 minutes daily over a period of several days. Defeated mice that were treated with LH dipeptide showed less social avoidance after the R-SDS. These mice also displayed less anxiety during the elevated plus maze test, as they spent more time in the open arms of the maze despite rodents typically having an aversion to open spaces. These results suggest that oral administration of LH dipeptide prevents depression-associated emotional disturbances.

Overall, the findings of this research show that repeated oral administrations of LH dipeptide suppress microglia activation and reduce depression-associated emotional disturbances in mice. It is hoped that these results can be replicated in humans, with the researchers proposing that consuming foods rich in LH dipeptide may be a safe, preventative method for maintaining good mental health.

Image credit: ©stock.adobe.com/au/Prostock-studio

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