The intricate balance of the brain relies not just on neurons but also on the complex interactions between nerve, immune, and stem cells. Recent studies have intriguing implications, suggesting that certain scents can significantly influence brain function and immune responses. Notably, researchers have established a connection between the loss of the sense of smell and the early onset of Alzheimer's disease, highlighting the potential importance of olfactory cues.

A new investigation has embarked on a groundbreaking journey to explore the relationship between an immunostimulatory odorant, particularly menthol, and its effects on both the immune system and cognitive abilities in mouse models of Alzheimer's disease and healthy counterparts. This study aims to deepen understanding of how scents like menthol might serve as therapeutic tools in combating cognitive decline.

The research findings have yielded promising results. Initially, the study observed that repeated short-term exposure to menthol odor enhanced the immune response in mice following immunization with ovalbumin. In models specifically engineered to mimic Alzheimer's disease, exposure to menthol not only improved cognitive function but also underscored the potential of olfactory stimulation in neuroprotection.

Moreover, the brief inhalation of menthol demonstrated a capacity to regulate the immune system, which could play a crucial role in preventing cognitive decline associated with neurodegenerative diseases. The researchers noted a significant reduction in the levels of IL-1β, a pivotal protein associated with inflammation and cognitive impairment. Interestingly, they found that blocking this protein using a pre-existing drug not only mitigated inflammation but also led to improved cognitive performance in affected mouse models.

Dr. Juan José Lasarte, the director of the Program of Immunology and Immunotherapy at Cima and the principal investigator of this study, emphasized the groundbreaking nature of the findings. He stated, “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.”

In a remarkable twist, the research revealed that consistent short exposures to menthol over six months had the potential to prevent cognitive decline in Alzheimer’s-afflicted mice. Even more intriguing was the observation that these brief exposures also enhanced cognitive abilities in healthy young mice, suggesting a broader applicability of menthol in neurocognitive health.

Furthermore, the study explored the role of T regulatory cells—immune cells that typically suppress immune responses. Researchers found that inhibiting these cells not only improved cognitive function in mice with Alzheimer’s but also provided cognitive benefits to healthy young mice. This dual effect opens up new avenues for understanding how immune modulation could influence cognitive health.

By exposing mice to menthol and blocking T regulatory cells, researchers observed a significant decrease in IL-1β levels, further solidifying the connection between immune function and cognitive performance in these models. Notably, a drug designed to target IL-1β, which has already received approval for treating autoimmune diseases, was shown to enhance cognitive capacity in both healthy and Alzheimer’s-afflicted mice.

Dr. Noelia Casares, a key researcher in the Immunology and Immunotherapy Program and first author of the article published on this study, remarked, “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 essential role in the prevention and treatment of Alzheimer’s and other diseases related to the central nervous system.”

These findings could pave the way for innovative therapeutic strategies leveraging olfactory stimuli to enhance cognitive function and combat neurodegenerative diseases like Alzheimer’s.

Journal Reference:

Noelia Casares, María Alfaro, Mar Cuadrado-Tejedor, Aritz Lasarte-Cia, Flor Navarro, Isabel Vivas, María Espelosin, Paz Cartas-Cejudo, Joaquín Fernández-Irigoyen, Enrique Santamaría, Ana García-Osta, Juan José Lasarte. 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. Front. Immunol. DOI: 10.3389/fimmu.2023.1130044