Mammals have the capacity to discriminate between an immense variety of odorants and pheromones. Pheromones are airborne chemical signals that are released by an individual into that affect the physiology and behavior of other members of the same species. Volatile and non-volatile compounds can both act as pheromones. Detection of odorants and pheromones is mediated through receptors in the main olfactory epithelium (MOE) and the vomeronasal organ (VNO). Sensing of pheromones by humans has been controversial because humans apparently do not have functional VNO. However, our recent data indicating that some mouse sexual activity is dependent on signaling mechanisms in the MOE suggests the interesting possibility that humans may also detect some pheromones through the MOE. This grant focuses on signal transduction mechanisms in the MOE and main olfactory bulb (MOB) that mediate detection of pheromones in the MOE as well as the survival of newly formed granule cells in the MOB caused by pheromone or odorant exposure. It is the central hypothesis of this grant that several types of signals detected through the MOE including volatile odorants and pheromones are mediated through the type 3 adenylyl cyclase (AC3), a calcium inhibited enzyme. We hypothesize that some pheromones or volatile odorants that contribute to male sexual activity and female selection of males are detected through receptors in the MOE coupled to AC3 by the G-coupling protein Golf. We hypothesize that pheromones and odorants activate signaling pathways in the MOE that generate signals propagated through axonal projections to the MOB. We propose that this leads to activation of the MAPK/CREB pathway in the MOB and increased survival of newly formed granule cells in the MOB. We also hypothesize that odorant- and pheromone-induced activation of MAPK in the MOB depends upon the calcium-stimulated degradation of SCN Circadian Oscillatory Protein (SCOP), a negative regulator of MAPK signaling in other neurons.
The chemosensory systems of mammals have the exquisite capacity to discriminate between an immense variety of odorants and pheromones. Perturbations of the olfactory system cause loss of appetite and poor nutrition, particularly with older patients. For example, the average human loses a significant proportion of their olfaction as they age, and olfactory dysfunction is associated with several aging-related neurodegenerative diseases including Alzheimer's and Parkinson's disease. Although controversial, there is also increasing evidence that humans may also detect some pheromones. Pheromones are "airborne chemical signals that are released by an individual into the environment that affect the physiology and behavior of other members of the same species". Volatile and non-volatile compounds can both act as pheromones. Pheromones provide information about gender and reproductive status, while also mediating social and sexual behaviors as well as neuro-endocrine changes. This grant focuses on mechanisms for detection of odorants and pheromones.
|Cao, Hong; Chen, Xuanmao; Yang, Yimei et al. (2016) Disruption of type 3 adenylyl cyclase expression in the hypothalamus leads to obesity. Integr Obes Diabetes 2:225-228|
|Stratigopoulos, George; Burnett, Lisa Cole; Rausch, Richard et al. (2016) Hypomorphism of Fto and Rpgrip1l causes obesity in mice. J Clin Invest 126:1897-910|
|Wang, Wenbin; Lu, Song; Li, Tan et al. (2015) Inducible activation of ERK5 MAP kinase enhances adult neurogenesis in the olfactory bulb and improves olfactory function. J Neurosci 35:7833-49|
|Chen, Xuanmao; Cao, Hong; Saraf, Amit et al. (2015) Overexpression of the type 1 adenylyl cyclase in the forebrain leads to deficits of behavioral inhibition. J Neurosci 35:339-51|
|Liu, Jack J; Chan, Guy C; Hecht, Avi S et al. (2014) Nasal saline irrigation has no effect on normal olfaction: a prospective randomized trial. Int Forum Allergy Rhinol 4:39-42|
|Zou, Junhui; Storm, Daniel R; Xia, Zhengui (2013) Conditional deletion of ERK5 MAP kinase in the nervous system impairs pheromone information processing and pheromone-evoked behaviors. PLoS One 8:e76901|
|Li, Tan; Pan, Yung-Wei; Wang, Wenbin et al. (2013) Targeted deletion of the ERK5 MAP kinase impairs neuronal differentiation, migration, and survival during adult neurogenesis in the olfactory bulb. PLoS One 8:e61948|
|Chen, Xuanmao; Xia, Zhengui; Storm, Daniel R (2013) Electroolfactogram (EOG) Recording in the Mouse Main Olfactory Epithelium. Bio Protoc 3:|
|Lim, Jae H; Davis, Greg E; Rue, Tessa C et al. (2012) Human sinonasal explant system for testing cytotoxicity of intranasal agents. Int Forum Allergy Rhinol 2:63-8|
|Zou, Junhui; Pan, Yung-Wei; Wang, Zhenshan et al. (2012) Targeted deletion of ERK5 MAP kinase in the developing nervous system impairs development of GABAergic interneurons in the main olfactory bulb and behavioral discrimination between structurally similar odorants. J Neurosci 32:4118-32|
Showing the most recent 10 out of 30 publications