An enhanced olfactory marker protein immunoreactivity in individual olfactory receptor neurons following olfactory bulbectomy may be related to increased neurogenesis

The mammalian olfactory neuroepithelium provides a unique system for understanding the regulation of neurogenesis by adult neural stem cells. Recently, mouse horizontal basal cells (HBCs) were identified as stem cells that regenerate olfactory receptor neurons (ORNs) and nonneuronal cell types only after extensive injury of the olfactory epithelium (OE). Here we report a broader spectrum of action for these cells. We show that even during normal neuronal turnover, HBCs actively generate neuronal and non-neuronal cells throughout adulthood. This occurs in a temporally controlled manner: an initial wave of HBC-derived neurogenesis was observed soon after birth, and a second wave of neurogenesis was observed at 4 months of age. Moreover, upon selective depletion of mature ORNs by olfactory bulbectomy, HBCs give rise to more neurons. Our findings demonstrate a crucial role for HBCs as multipotent progenitors in the adult OE, acting during normal neuronal turnover as well as in acute regeneration upon injury. STEM CELLS

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“…5G with Fig. 2J), as was reported previously [29], yet several β‐gal + /OMP + cells were observed (Fig. 5G, arrow).…”

Section: Resultssupporting

confidence: 87%

Horizontal Basal Cells Are Multipotent Progenitors in Normal and Injured Adult Olfactory Epithelium

et al. 2008

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“…This phenomenon could be due to a reduction in the survival of basal cells and immature olfactory sensory neurons or the upregulation of either NPY Y1 receptors on basal cells or positive regulators of neurogenesis to compensate for the decrease in basal cells. Possibilities of positive regulators include fibroblast growth factor and transforming growth factor [40], amidated peptides [41], leukemia inhibitory factor [42] and OMP [43]. The overall implications of these results are that an appropriate population of neural stem cells is maintained by IP3R3 + microvillous cells by the production and release of trophic factor NPY.…”

Section: Discussionmentioning

confidence: 97%

An IP3R3- and NPY-Expressing Microvillous Cell Mediates Tissue Homeostasis and Regeneration in the Mouse Olfactory Epithelium

et al. 2013

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Calcium-dependent release of neurotrophic factors plays an important role in the maintenance of neurons, yet the release mechanisms are understudied. The inositol triphosphate (IP3) receptor is a calcium release channel that has a physiological role in cell growth, development, sensory perception, neuronal signaling and secretion. In the olfactory system, the IP3 receptor subtype 3 (IP3R3) is expressed exclusively in a microvillous cell subtype that is the predominant cell expressing neurotrophic factor neuropeptide Y (NPY). We hypothesized that IP3R3-expressing microvillous cells secrete sufficient NPY needed for both the continual maintenance of the neuronal population and for neuroregeneration following injury. We addressed this question by assessing the release of NPY and the regenerative capabilities of wild type, IP3R3+/−, and IP3R3−/− mice. Injury, simulated using extracellular ATP, induced IP3 receptor-mediated NPY release in wild-type mice. ATP-evoked NPY release was impaired in IP3R3−/− mice, suggesting that IP3R3 contributes to NPY release following injury. Under normal physiological conditions, both IP3R3−/− mice and explants from these mice had fewer progenitor cells that proliferate and differentiate into immature neurons. Although the number of mature neurons and the in vivo rate of proliferation were not altered, the proliferative response to the olfactotoxicant satratoxin G and olfactory bulb ablation injury was compromised in the olfactory epithelium of IP3R3−/− mice. The reductions in both NPY release and number of progenitor cells in IP3R3−/− mice point to a role of the IP3R3 in tissue homeostasis and neuroregeneration. Collectively, these data suggest that IP3R3 expressing microvillous cells are actively responsive to injury and promote recovery.

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“…It was the objective of these studies to investigate the presence of DAT in the nasal mucosa and determine its role in dopamine transport across the olfactory and nasal respiratory tissues. Bovine tissues were selected for investigation since the olfactory and nasal respiratory tissues are easily distinguishable, and numerous investigations of olfactory neuronal structure and function have been conducted using these tissues (Menco, 1980;Carr et al, 1998). Since the nasal respiratory mucosa does not contain olfactory neurons, the presence of DAT in this tissue was also investigated.…”

Section: Introductionmentioning

confidence: 99%

Role of dopamine transporter (DAT) in dopamine transport across the nasal mucosa

et al. 2006

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An enhanced olfactory marker protein immunoreactivity in individual olfactory receptor neurons following olfactory bulbectomy may be related to increased neurogenesis

Cited by 39 publications

References 24 publications

Horizontal Basal Cells Are Multipotent Progenitors in Normal and Injured Adult Olfactory Epithelium

Horizontal Basal Cells Are Multipotent Progenitors in Normal and Injured Adult Olfactory Epithelium

An IP3R3- and NPY-Expressing Microvillous Cell Mediates Tissue Homeostasis and Regeneration in the Mouse Olfactory Epithelium

Role of dopamine transporter (DAT) in dopamine transport across the nasal mucosa

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