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Could Menthol Be the Key to Alzheimer’s Disease?

A Spanish study suggests a potential new avenue for Alzheimer’s treatment. Inhaling menthol improves mental abilities.

The research demonstrates that menthol exposure in mice with Alzheimer’s disease leads to improved cognitive function. It appears the menthol disrupts the progression of the disease by reducing interleukin-1-beta (IL-1β) protein levels. This protein plays a critical role in regulating the body’s inflammatory response, which can be beneficial in moderation but detrimental when uncontrolled.

These findings suggest that specific scents may be harnessed for therapeutic purposes in Alzheimer’s disease. By understanding the intricate link between odors and the brain and immune system’s response, researchers can potentially develop novel treatments to promote cognitive health.

Immunologist Juan José Lasarte of the Center for Applied Medical Research (CIMA) in Spain investigated the olfactory system’s influence on the immune and central nervous systems. The research confirmed menthol’s immunostimulatory properties in animal models.

Interestingly, researchers observed that short, six-month exposures to menthol not only prevented cognitive decline in mice with Alzheimer’s but also improved cognitive function in healthy young mice. Building on previous findings regarding menthol’s immune-boosting properties, this study demonstrated its potential impact on cognitive health.

In mice with Alzheimer’s, a six-month menthol regimen halted the deterioration of cognitive and memory abilities. Additionally, menthol appeared to regulate interleukin-1-beta (IL-1β) protein levels in the brain, bringing them back to a healthy range.

Similar effects were observed when researchers artificially reduced T regulatory (Treg) cells, suggesting a potential future treatment pathway. Neuroscientist Ana Garcia-Osta of CIMA noted, “Both menthol exposure and Treg cell blockade caused a decrease in IL-1β, a protein potentially linked to the observed cognitive decline in these models.”

Furthermore, specifically blocking this protein with a medication used for autoimmune diseases also improved cognitive function in both healthy and Alzheimer’s mice. These findings suggest promise for novel Alzheimer’s treatments that utilize olfactory stimulation or target the IL-1β protein.

A well-established connection exists between our sense of smell and both the immune and nervous systems. Though the complexities of this relationship remain under investigation, it’s clear that our olfactory system significantly influences brain function. Specific scents are believed to trigger responses within the brain, leading to chemical reactions that impact memory, emotion, and various other processes.

Interestingly, diseases affecting the central nervous system, like Alzheimer’s, Parkinson’s, and schizophrenia, often present with a diminished sense of smell. This new research offers promising initial findings, but further studies involving human subjects, alongside continued investigation in mice, are crucial.

“This research represents a significant advancement in understanding the link between the immune system, the central nervous system, and the sense of smell. The results suggest a potentially important role for odors and immune modulators in the prevention and treatment of Alzheimer’s disease and other central nervous system disorders.”

immunologist Noelia Casares of CIMA.

https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1130044/full

Abstract

A complex network of interactions exists between the olfactory, immune and central nervous systems. In this work we intend to investigate this connection through the use of an immunostimulatory odorant like menthol, analyzing its impact on the immune system and the cognitive capacity in healthy and Alzheimer’s Disease Mouse Models. We first found that repeated short exposures to menthol odor enhanced the immune response against ovalbumin immunization. Menthol inhalation also improved the cognitive capacity of immunocompetent mice but not in immunodeficient NSG mice, which exhibited very poor fear-conditioning. This improvement was associated with a downregulation of IL-1β and IL-6 mRNA in the brain´s prefrontal cortex, and it was impaired by anosmia induction with methimazole. Exposure to menthol for 6 months (1 week per month) prevented the cognitive impairment observed in the APP/PS1 mouse model of Alzheimer. Besides, this improvement was also observed by the depletion or inhibition of T regulatory cells. Treg depletion also improved the cognitive capacity of the APPNL-G-F/NL-G-F Alzheimer´s mouse model. In all cases, the improvement in learning capacity was associated with a downregulation of IL-1β mRNA. Blockade of the IL-1 receptor with anakinra resulted in a significant increase in cognitive capacity in healthy mice as well as in the APP/PS1 model of Alzheimer´s disease. These data suggest an association between the immunomodulatory capacity of smells and their impact on the cognitive functions of the animals, highlighting the potential of odors and immune modulators as therapeutic agents for CNS-related diseases.

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