Anxiety- and Depression-Like States Lead to Pronounced Olfactory Deficits and Impaired Adult Neurogenesis in Mice

作者：Siopi Eleni; Denizet Marie; Gabellec Marie Madeleine; de Chaumont Fabrice; Olivo Marin Jean Christophe; Guilloux Jean Philippe; Lledo Pierre Marie^*; Lazarini Francoise

来源：Journal of Neuroscience, 2016, 36(2): 518-531.

DOI：10.1523/JNEUROSCI.2817-15.2016

• corticosterone
• dentate gyms
• olfactory bulb
• olfactory epithelium
• serotonin
• subventricular zone

Numerous clinical reports underscore the frequency of olfactory impairments in patients suffering from major depressive disorders (MDDs), yet the underlying physiopathological mechanisms remain poorly understood. We hypothesized that one key link between olfactory deficits and MDD lies in hypercortisolemia, a cardinal symptom of MDD. Corticosterone (CORT) is known to negatively correlate with hippocampal neurogenesis, yet its effects on olfactory neurogenesis and olfaction remain unknown. Here we used a rodent model of anxiety/depression-like states, which is based on chronic CORT administration and studied the effects of the antidepressant fluoxetine (FLX) on behavior, olfaction, and adult neurogenesis in the dentate gyrus (DG), olfactory bulb (OB), and the olfactory epithelium (OE). Chronic CORT had no effect on cell proliferation in the OE or on olfactory sensory neurons projecting to the OB, but induced pronounced deficits in olfactory acuity, fine discrimination of odorants and olfactory memory. These alterations were accompanied by a significant decrease in the number of adult-born neurons in both the DG and OB. Remarkably, FLX not only reversed depression-like states as expected, but also improved olfactory acuity, memory, and restored impaired adult neurogenesis. However, fine olfactory discrimination was not restored. Morphological analysis of adult-born neurons in both the DG and the OB showed that dendritic complexity was not significantly affected by CORT, but was increased by FLX. These findings demonstrate an essential role for glucocorticoids in triggering olfactory impairments in MDD and highlight a novel therapeutic effect of FLX.

• 出版日期2016-1-13