Abstract
Type 3 adenylyl cyclase (Adcy3) is localized to the cilia of olfactory sensory neurons (OSNs) and is an essential component of the olfactory cyclic adenosine monophosphate (cAMP) signaling pathway. Although the role of this enzyme in odor detection and axonal projection in OSNs was previously characterized, researchers will still have to determine its function in the maturation of postnatal OSNs and olfactory cilium ultrastructure. Previous studies on newborns showed that the anatomic structure of the main olfactory epithelium (MOE) of Adcy3 knockout mice (Adcy3-/-) is indistinguishable from that of their wild-type littermates (Adcy3+/+), whereas the architecture and associated composition of MOE are relatively underdeveloped at this early age. The full effects of sensory deprivation on OSNs may not also be exhibited in such age. In the present study, following a comparison of postnatal OSNs in seven-, 30-, and 90-day-old Adcy3-/- mice and wild-type controls (Adcy3+/+), we observed that the absence of Adcy3 leads to cumulative defects in the maturation of OSNs. Upon aging, Adcy3-/- OSNs exhibited increase in immature cells and reduction in mature cells along with elevated apoptosis levels. The density and ultrastructure of Adcy3-/- cilia were also disrupted in mice upon aging. Collectively, our results reveal an indispensable role of Adcy3 in postnatal maturation of OSNs and maintenance of olfactory cilium ultrastructure in mice through adulthood.
Highlights
The main olfactory epithelium (MOE) is a pseudostratified epithelial structure required for odor perception in mammals (Beites et al, 2005)
We examined the olfactory sensory neurons (OSNs) of Adcy3−/− mice and Adcy3+/+ littermates after seven, 30, and 90 postnatal days and demonstrated that the absence of Adcy3 induced the formation of thinner MOE and increased loss of mature olfactory sensory neurons (mOSNs) along with elevated levels of apoptosis
By using qRT-polymerase chain reaction (PCR) analysis, we confirmed that the Adcy3 expression levels in MOEs of P7, P30, and P90 Adcy3−/− mice are significantly lower compared with those of Adcy3+/+ mice with the same ages (Figure 1I)
Summary
The main olfactory epithelium (MOE) is a pseudostratified epithelial structure required for odor perception in mammals (Beites et al, 2005). The neural stem cells located in the basal epithelium give rise to olfactory sensory neurons (OSNs) (Jang et al, 2014). Several million OSNs, consisting of immature olfactory sensory neurons (iOSNs) and mature olfactory sensory neurons (mOSNs), are situated in the middle of the MOE. OSNs undergo caspasemediated apoptosis at all stages of their life cycle (Mahalik, 1996). These cells are subsequently replenished by newly generated OSNs from the division of the basal stem cells to maintain epithelial homeostasis
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