The research conducted by Noelia Casares, Juan José Lasarte, and their team at the University of Navarra investigates the intricate relationship between the olfactory system, immune response, and cognitive function in both healthy mice and Alzheimer's Disease (AD) mouse models. They focused on how menthol inhalation, a known immunostimulant, affects the cognitive performance of these mice. Through their experiments, they found that short-term exposure to menthol enhanced cognitive function in healthy, immunocompetent mice, but not in immunodeficient mice, implying a key role of the immune system in cognitive improvement. The beneficial effects were associated with a reduction in the inflammatory markers IL-1β and IL-6 in the prefrontal cortex, both of which are linked to cognitive decline in neurodegenerative diseases.
In Alzheimer's mouse models, including APP/PS1 and APPNL-G-F strains, prolonged menthol exposure for six months significantly prevented cognitive deterioration typically seen in these models. This effect was paralleled by a similar improvement in learning capacity when regulatory T cells (Tregs) were depleted. The researchers demonstrated that blocking the IL-1 receptor using the drug anakinra yielded notable cognitive enhancements, reinforcing the idea that inflammatory cytokines, particularly IL-1β, play a pivotal role in regulating cognitive decline in both healthy and AD-affected brains. Importantly, these cognitive improvements occurred independently of amyloid plaque reduction, suggesting that the therapeutic potential of menthol or Treg depletion operates through mechanisms separate from amyloid pathology.
This study points to a broader implication that smells, particularly menthol, might have immunomodulatory properties capable of influencing cognitive health, potentially offering a novel avenue for treating central nervous system (CNS) diseases like Alzheimer's. While the exact mechanisms behind the interaction between olfaction, the immune system, and brain function remain unclear, the results underscore the importance of investigating how immune modulation through olfactory stimuli or the manipulation of immune cells could provide therapeutic benefits for cognitive impairment. The findings encourage further exploration of using immune-targeting therapies, such as IL-1β inhibitors or Treg modulation, in the treatment of Alzheimer's and other neurodegenerative disorders.
