This study opens the door to developing therapies based on stimulating and training the olfactory system to prevent or alleviate the effects of Alzheimer's and other diseases of the central nervous system. Credit: Neuroscience News
Menthol Inhalation May Boost Cognitive Ability in Alzheimer’s
Summary: Menthol inhalation can improve cognitive abilities in animal models of Alzheimer’s disease, researchers report.
Short, repeated exposure to menthol can modulate the immune system and prevent cognitive decline commonly seen in Alzheimer’s.
Researchers found that the smell of menthol reduced the level of interleukin-1-beta (IL-1b), a protein crucial to the inflammatory response. By inhibiting this protein with a specific drug, cognitive abilities were also improved in the mice models.
This research suggests the possibility of therapies based on stimulating the olfactory system to counteract Alzheimer’s and other central nervous system diseases.
Researchers discovered that inhaling menthol improves cognitive abilities in animal models of Alzheimer’s disease, potentially preventing the cognitive decline typical of the disease.
The study found that menthol aroma led to a reduction in the level of interleukin-1-beta (IL-1b), a protein that mediates the inflammatory response. This reduction in IL-1b levels was associated with improved cognitive abilities in both healthy mice and those with Alzheimer’s.
The research suggests the potential for odors and immune modulators as therapeutic agents in treating Alzheimer’s disease and other conditions of the central nervous system, opening a new avenue for developing therapies based on stimulating and training the olfactory system.
Source: Universidad de Navarra
Researchers from Cima University of Navarra (Spain) have shown in animal models of Alzheimer’s disease that inhaling menthol improves cognitive ability.
This study discovered that repeated short exposures to this substance can modulate the immune system and prevent the cognitive deterioration typical of this neurodegenerative disease.
When analyzing its mechanism of action, they observed that when smelling this aroma, the level of interleukin-1-beta (IL-1b), a critical protein mediating the inflammatory response, was reduced.
Furthermore, by inhibiting this protein with a drug approved for the treatment of some autoimmune diseases, they were also able to improve cognitive ability in these diseased mice.
This research highlights the potential of odors and immune modulators as therapeutic agents. Furthermore, it opens the door to developing therapies based on stimulating and training the olfactory system to prevent or alleviate the effects of Alzheimer’s and other diseases of the central nervous system.
Frontiers in Immunology published the results of this study in its latest issue.
Brain, smell, and immune system connection
The functional balance of the brain depends on complex interactions between various types of nerve cells, immune cells, and neural stem cells. In this complex web of interactions, several studies have addressed the immunomodulatory and neurological effects of odorants.
Other previous works have also shown a correlation between the loss of the sense of smell and the appearance of the first symptoms of Alzheimer’s disease.
“We have focused on the olfactory system’s role in the immune and central nervous systems, and we have confirmed that menthol is an immunostimulatory odor in animal models.
“But, surprisingly, we observed that short exposures to this substance for six months prevented cognitive decline in the mice with Alzheimer’s and, what is most interesting, also improved the cognitive ability of healthy young mice,” says Dr Juan José Lasarte.
Another result noted by the researchers is that “blocking the activity of T regulatory cells, one type of immune cells with immunosuppressive activity, also improved the cognitive ability of mice with Alzheimer’s disease and also caused a clear benefit in the cognitive ability of healthy young mice,” explains Dr. Ana García-Osta.
“Both menthol exposure and Treg cell blockade caused a decrease in IL-1b, a protein that could be behind the cognitive decline observed in these models. In addition, the specific blockade of this protein with a drug used in treating some autoimmune diseases also improved the cognitive capacity of healthy mice and mice with Alzheimer’s”.
“This study is an important step toward understanding the connection between the immune system, the central nervous system and smell, as the results suggest that odors and immune modulators may play an important role in the prevention and treatment of Alzheimer’s.” and other diseases related to the central nervous system,” points out Dr. Noelia Casares.
Funding: The Government of Navarra and the Ministry of Economy and Competitiveness financed 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, a Navarrabiomed researcher.
This consortium aims to study the olfactory function in aging and develop new immunomodulatory therapies to slow down the development of neurodegenerative diseases.
Improvement of cognitive function in wild-type and Alzheimer’s disease mouse models by the immunomodulatory properties of menthol inhalation or by depletion of T regulatory cells
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.