Phosphoinositide and Erk signaling pathways mediate activity‐driven rodent olfactory sensory neuronal survival and stress mitigation

Abstract

Olfactory sensory neurons (OSNs) are the initial site for olfactory signal transduction. Therefore, their survival is essential to olfactory function. In the current study, we demonstrated that while odorant stimulation promoted rodent OSN survival, it induced generation of reactive oxygen species in a dose- and time-dependent manner as well as loss of membrane potential and fragmentation of mitochondria. The MEK-Erk pathway played a critical role in mediating these events, as its inhibition decreased odorant stimulation-dependent OSN survival and exacerbated intracellular stress measured by reactive oxygen species generation and heat shock protein 70 (Hsp70) expression. The phosphoinositide pathway, rather than the cyclic AMP pathway, mediated the odorant-induced activation of the MEK-Erk pathway. These findings provide important insights into the mechanisms of activity-driven OSN survival, the role of the phosphoinositide pathway in odorant signaling, and demonstrate that odorant detection and odorant stimulation-mediated survival proceed via independent signaling pathways. This mechanism, which permits independent regulation of odorant detection from survival signaling, may be advantageous if not diminished by repeated or prolonged odor exposure.

Deletion of Type 3 Adenylyl Cyclase Perturbs the Postnatal Maturation of Olfactory Sensory Neurons and Olfactory Cilium Ultrastructure in Mice

“…The similar appearance raised the possibility that odorant detection and stimulation-mediated OSN survival might be processed via independent signaling pathways (Kim et al, 2015). However, a limitation of these studies involved using 1-day-old pups as cAMP-cascade-component knockout mice.…”

Olfactory receptor 10J5 responding to α-cedrene regulates hepatic steatosis via the cAMP–PKA pathway

“…To determine whether α-cedrene activates ORs and relays olfactory signaling, we measured intracellular levels of cAMP, the major second messenger of olfactory signaling, and of Ca 2+ in the primary rat olfactory sensory neurons (OSNs) 16 , 17 . α-Cedrene increased intracellular cAMP level similarly to the action of odorant mixture in OSNs (Fig.…”

SB203580, a p38MAPK inhibitor, attenuates olfactory dysfunction by inhibiting OSN apoptosis in AR mice (activation and involvement of the p38 mitogen‐activated protein kinase in olfactory sensory neuronal apoptosis of OVA‐induced allergic rhinitis)

“…Inhibition of OSN apoptosis may be a feasible treatment (Kern et al, 2004) for olfactory dysfunction (Hutch & Hegg, 2016;Kim et al, 2015). OSNs are the initial site for olfactory signal transduction.…”