Menthol inhalation improves cognitive ability in animal models of Alzheimer’s disease


Researchers from the Cima University of Navarra (Spain) have shown in animal models of Alzheimer’s disease that inhaling menthol improves cognitive ability. This study discovered that short, repeated exposure to this substance can modulate the immune system and prevent the cognitive decline typical of this neurodegenerative disease. Analyzing its mechanism of action, they noted that when this scent was sniffed, the level of interleukin-1 beta (IL-1b), an important protein that mediates the inflammatory response, decreased. Moreover, by inhibiting this protein with a drug approved to treat certain autoimmune diseases, they were also able to improve cognitive ability in these diseased mice.

This research highlights the potential of aromatherapy and immunomodulators as therapeutic agents. Moreover, it opens the door to developing therapies based on stimulating and training the olfactory system to prevent or mitigate the effects of Alzheimer’s disease and other diseases of the central nervous system. Frontiers in Immunology The results of this study were published in its latest issue.

The brain, smell, and immune system connection

The functional homeostasis of the brain depends on complex interactions between different types of neurons, immune cells, and neural stem cells. In this complex web of interactions, many studies have addressed the immunomodulatory and neuroprotective effects of odor. Other previous work has also shown a relationship between loss of the sense of smell and the onset of the first symptoms of Alzheimer’s disease.

We have focused on the role of the olfactory system in the immune system and the central nervous system, and have confirmed that menthol is an immunostimulant odorant in animal models. But, surprisingly, we noticed that a short exposure to this substance for six months prevented cognitive decline in mice with Alzheimer’s disease and, more interestingly, also improved the cognitive ability of healthy young mice.

Dr. Juan Jose Lasarte, director of the Immunology and Immunotherapy Program at Cima and lead author of the investigation

Another finding the researchers noted was that “blocking the activity of regulatory T cells, one type of immune cell with immunosuppressive activity, also improved the cognitive ability of mice with Alzheimer’s disease, and led to a clear benefit in the cognitive ability of healthy young mice,” explains Dr. Ana Garcia-Aosta, researcher in the Sima Gene Therapy Program for Neurological Diseases and co-lead author of this work. “Both exposure to menthol and blockade of Treg cells caused a decrease in IL-1b, a protein that could be behind the cognitive decline observed in these models. In addition, specific blockade of this protein with a drug used in the treatment of certain autoimmune diseases also improved cognitive ability. of healthy mice and mice with Alzheimer’s disease.

“This study is an important step towards understanding the relationship between the immune system, the central nervous system, and odor, as the findings suggest that odors and immune modulators may play an important role in the prevention and treatment of Alzheimer’s disease.” and other diseases related to the central nervous system,” notes Dr. Noelia Casares, also a researcher in the Immunology and Immunotherapy Program and first author of the article.

The government of Navarre and the Ministry of Economy and Competitiveness funded this work. It is part of the Instituto de Investigación Santiaria de Navarra (IdiSNA). It is also part of the INNOLFACT project, a multicenter consortium coordinated by Dr. Enrique Santamaría, researcher at Navarabiomed. This consortium aims to study olfactory function in aging and to develop novel immunomodulatory therapies to slow the progression of neurodegenerative diseases.


Journal reference:

Casares, N.; et al. (2023). Improvement of cognitive function in wild-type mouse models of Alzheimer’s disease by the immunomodulatory properties of menthol inhalation or by depletion of T regulatory cells. Frontiers in Immunology.


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