Reduced neurogenesis and pre-synaptic dysfunction in the olfactory bulb of a rat model of depression

Abstract

A variety of evidence has a connection with hippocampal neurogenesis in the pathophysiology of depression. However, whether other neurogenic regions in the adult central nervous system would likewise be involved is a highly interesting question. The olfactory bulb (OB) is one of the post-developmental neurogenesis areas in the adult mammalian brain. Clinical studies have shown a decreased olfactory sensitivity in depressed patients, and a recent study disclosed cases of reduced OB volume in acute major depression, indicating the OB may be also affected. Here, animal models are superior to human studies, which may provide further insight into such complex processes. We therefore investigated OB neurogenesis using a chronic unpredictable mild stress (CUMS) rat model of depression. Considering the functional analysis of adult neurogenesis which has been carried out at the synaptic level as well as animal behavior level, we detected pre-synaptic and olfactory function in the OB of rats after 4 weeks of chronic stress. Immunohistochemistry and Western blot analysis showed a dramatic reduction of immature neurons marked by polysialylated neural cell adhesion molecule and doublecortin as well as mature neurons labeled by neuronal nuclei. Moreover, chronic stress down-regulated the expression of synaptophsin but up-regulated syntaxin in the OB, as demonstrated by Western blot, whereas a significant variation at the mRNA level was lacking. Notably, in the rat model of depression, both a decreased OB volume and olfactory dysfunction were present at the same time, which is consistent with clinical findings in depressed patients. In summary, reduced OB neurogenesis and pre-synaptic dysfunction were observed in the rat model, which may at least in part correspond to the reduced OB volume and olfactory malfunction in patients suffering from depression.