Age-Related In Vivo Structural Changes in the Male Mouse Olfactory Bulb and Their Correlation with Olfactory-Driven Behavior

SIMPLE SUMMARY: In humans and mice, the olfactory system is linked to areas of the brain that modulate behavior. Malfunctions of the olfactory system were described in many neurological and psychiatric diseases, including Alzheimer’s and Parkinson’s disease, depression, and mood disorders. Some of these diseases are common in aging persons; hence, it is relevant to know how the olfactory bulb, the first olfactory center in the brain, changes with age in its structure, and how these changes may be related to behavioral modifications. Since most of the experimental work is performed in mice, we studied young and elderly mice with a battery of behavioral tests to describe the differences in motor, olfactory, cognitive, and emotional performance. Then, mice underwent magnetic resonance imaging to describe the differences between olfactory bulbs of young and elderly mice. Lastly, we selected the behavioral variables more predictive of the differences between young and elderly mice and correlated them with the most predictive magnetic resonance variables. Elderly mice were less scared than young mice by new environments, and their olfactory bulb differed in two structural variables, which correlated with three anxiety measures. These data suggest a new direction for human aging studies, on the link between the olfactory bulb and behavior. ABSTRACT: Olfactory areas in mammalian brains are linked to centers that modulate behavior. During aging, sensitivity to odors decreases and structural changes are described in olfactory areas. We explored, in two groups of male mice (young and elderly, 6 and 19 months old, respectively), the link between the changes in olfactory bulb structure, detected with magnetic resonance imaging, and behavioral changes in a battery of tests on motor, olfactory, cognitive performance, and emotional reactivity. The behavioral pattern of elderly mice appears less anxious, being less scared by new situations. Additionally, the olfactory bulb of young and elderly mice differed in two variables derived from magnetic resonance imaging (fractional anisotropy and T2 maps). A random forest approach allowed to select the variables most predictive of the differences between young and elderly mice, and correlations were found between three behavioral variables indicative of anxious behavior and the two magnetic resonance variables mentioned above. These data suggest that in the living mouse, it is possible to describe co-occurring age-related behavioral and structural changes in the olfactory bulb. These data serve as a basis for studies on normal and pathological aging in the mouse, but also open new opportunities for in vivo human aging studies.