Summary: Menthol inhalation can improve cognitive abilities in animal models of Alzheimers disease, researchers report.

Short, repeated exposure to menthol can modulate the immune system and prevent cognitive decline commonly seen in Alzheimers.

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 Alzheimers and other central nervous system diseases.

Key Facts:

Source: Universidad de Navarra

Researchers fromCima University of Navarra(Spain) have shown in animal models ofAlzheimers diseasethat 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 ofinterleukin-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 Alzheimers and other diseases of the central nervous system.

Frontiers in Immunologypublished the results of this study in its latest issue.

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 Alzheimers disease.

We have focused on the olfactory systems 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 Alzheimers and, what is most interesting, also improved the cognitive ability of healthy young mice, says DrJuan Jos 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 Alzheimers disease and also caused a clear benefit in the cognitive ability of healthy young mice, explains Dr.Ana Garca-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 Alzheimers.

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 Alzheimers. 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 Investigacin Santiaria de Navarra (IdiSNA). It is also part of the INNOLFACT project, a multicenter consortium coordinated by Dr Enrique Santamara, 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.

Author: Miriam SalcedoSource: Universidad de NavarraContact: Miriam Salcedo Universidad de NavarraImage: The image is credited to Neuroscience News

Original Research: Open access.Improvement of cognitive function in wild-type and Alzheimers disease mouse models by the immunomodulatory properties of menthol inhalation or by depletion of T regulatory cells by Casares Noelia et al. Frontiers in Immunology

Abstract

Improvement of cognitive function in wild-type and Alzheimers 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 Alzheimers 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-1 and IL-6 mRNA in the brains 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-FAlzheimers mouse model. In all cases, the improvement in learning capacity was associated with a downregulation of IL-1 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 Alzheimers 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.

Link:
Menthol Inhalation May Boost Cognitive Ability in Alzheimer's - Neuroscience News