Effects of adenoviral vector-mediated BDNF expression on the bulbectomy-induced apoptosis of olfactory receptor neurons

Isoyama, Kyoko; Nagata, Hiroshi; Shino, Yuji; Isegawa, Naohisa; Arimoto, Yukiko; Koda, Masao; Kumahara, Keiichiro; Okamoto, Yoshitaka; Shirasawa, Hiroshi

doi:10.1016/j.molbrainres.2004.06.031

Cited by 11 publications

(6 citation statements)

References 23 publications

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“…1(K)]. As the normal level of apoptosis of OSNs in the olfactory epithelium of the wildtype mice that can be detected by the TUNEL assay is known to be rather low or almost null (e.g., Suzuki, 1998;Voyron et al, 1999;Cowan and Roskams, 2002;Moon and Baker, 2002;Isoyama et al, 2004;Sakamoto et al, 2007), these results point out that many cells in the mutant mice but not in the wildtype mice continually undergo apoptosis. Furthermore, quantitative evaluation of thickness of the olfactory epithelia demonstrated that the epithelium of the null mutant mice was significantly thinner [ Fig.…”

Section: Histochemical Analyses Of the Olfactory Epitheliamentioning

confidence: 91%

“…Odorant-dependent survival via MAPK and CREB has been reported (Watt et al, 2004), and the role of leukemia inhibitory factor, a factor that functions in the immune system, in the survival of OSNs has also been reported (Getchell et al, 2002;Bauer et al, 2003;Moon et al, 2008). In addition, BCL2 and BDNF (brain-derived neurotrophic factor) appear to suppress the experimentally induced degeneration of OSNs (Jourdan et al, 1998;Hayward et al, 2004;Isoyama et al, 2004), and BAX is suggested to be involved in the promotion of apoptosis induced by bulbectomy (Robinson et al, 2003). It is expected to clarify relationships between BCL6 and these survival-promoting and apoptosis-promoting molecules.…”

Section: Anti-apoptotic Function Of Bcl6 In the Olfactory Epitheliummentioning

confidence: 99%

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The proto‐oncogene BCL6 promotes survival of olfactory sensory neurons

Otaki

Hatano

Matayoshi

et al. 2010

Developmental Neurobiology

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For the mammalian olfactory epithelium to continually detect odorant, neuronal survival, apoptosis, and regeneration must be coordinated. Here, we showed that the proto-oncogene BCL6, which encodes a transcriptional repressor required for lymphocyte terminal differentiation, contributes to the survival of olfactory sensory neurons (OSNs). In the olfactory epithelia of the BCL6 null mutant mice, many OSNs were positive for both OMP and GAP43. The epithelium was relatively thinner, showing many apoptotic signals. These characters were phenotypically similar to those of the wild-type mice treated with nasal lectin irrigation, which acutely induces apoptosis of OSNs. Odorant receptors were expressed normally in the epithelia of the mutant mice, and their overall expression profile based on DNA microarray analyses was roughly similar to that of the apoptosis-induced olfactory epithelia of the wild-type mice. Experimental increase of BCL6 together with green fluorescent protein in OSNs using adenovirus-mediated gene transfer made the epifluorescence last longer than the control fluorescence without exogenous BCL6 after the nasal lectin irrigation, indicating that BCL6 made the infected neurons survive longer. We conclude that BCL6 plays an active role in the survival of OSNs as an anti-apoptotic factor and confers immature OSNs enough time to fully differentiate into mature ones.

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Section: Histochemical Analyses Of the Olfactory Epitheliamentioning

confidence: 91%

Section: Anti-apoptotic Function Of Bcl6 In the Olfactory Epitheliummentioning

confidence: 99%

The proto‐oncogene BCL6 promotes survival of olfactory sensory neurons

Otaki

Hatano

Matayoshi

et al. 2010

Developmental Neurobiology

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“…However, this unique ability deteriorates with age and in response to various toxic factors, including smoking, viruses, inflammation, medication and environmental factors, leading to olfactory dysfunction (6,7) . Although many approaches, including vitamin A, zinc and various growth factors, have promising findings, they have not been applied as clinical practice methods for olfactory dysfunction (7)(8)(9)(10) . Topical or systemic application of glucocorticoids is a common clinical treatment, but its therapeutic effect is controversial.…”

Section: Introductionmentioning

confidence: 99%

Chitosan films promote formation of olfactory neurospheres and differentiation of olfactory receptor neurons

Young

Wang

et al. 2018

Rhin

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Background: Olfactory dysfunction significantly impairs the life quality of patients. Therefore, a model needs to be developed for anosmia. Chitosan is a biodegradable natural polysaccharide that has been widely studied for regenerative purposes in the nervous system. However, whether chitosan promotes differentiation of olfactory receptor neurons or regulates formation of neurospheres in the olfactory system remains unexplored. Methodology: Olfactory neuroepithelial cells were isolated from embryonic wistar rats on day 17, and cultured on controls and chitosan films for 12 days. The effects of treatment were assessed using immunocytochemistry, quantitative polymerase chain reaction and western blots following culturing. The substrate of poly-L-lysine-co-laminin was adopted as a control. Results: In contrast to the flat layer on controls, olfactory neuroepithelial cells form olfactory neurospheres on chitosan films with steadily increasing diameter. The olfactory neurospheres contain basal cells, as well as immature and mature olfactory receptor neurons. The expression level of olfactory marker protein is higher on chitosan films than those on controls in gene and protein levels, and the olfactory transduction elements also express a similar trend. Mature olfactory receptor neurons are found predominantly at the periphery of the olfactory neurospheres. Conclusions: Chitosan films not only facilitate formation of olfactory neurospheres, but also promote differentiation of olfactory receptor neurons. Chitosan is a potential biomaterial to establish an in vitro culture model to treat olfactory dysfunction in future.

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“…The basal cells have stemness/progenitor characteristics and play essential roles in epithelial remodeling [2] . Both the OE and AE have indirect contact with the external environment and many factors, including injury, mechanical stress, transcription factors and growth factors, regulate their neurogenesis and epithelial regeneration [3] , [4] , [5] , [6] , [7] , [8] , [9] . Thus, determining which receptors and sensors are expressed in these basal cells could contribute to the understanding of their function and regulation.…”

Section: Introductionmentioning

confidence: 99%

Basal cells express functional TRPV4 channels in the mouse nasal epithelium

Ueda

Hoshikawa

Shibata

et al. 2015

Biochemistry and Biophysics Reports

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Basal cells in the nasal epithelium (olfactory and airway epithelia) are stem/progenitor cells that are capable of dividing, renewing and differentiating into specialized cells. These stem cells can sense their biophysical microenvironment, but the underlying mechanism of this process remains unknown. Here, we demonstrate the prominent expression of the transient receptor potential vanilloid type 4 (TRPV4) channel, a Ca2+-permeable channel that is known to act as a sensor for hypo-osmotic and mechanical stresses, in the basal cells of the mouse nasal epithelium. TRPV4 mRNA was expressed in the basal portions of the prenatal mouse nasal epithelium, and this expression continued into adult mice. The TRPV4 protein was also detected in the basal layers of the nasal epithelium in wild-type but not in TRPV4-knockout (TRPV4-KO) mice. The TRPV4-positive immunoreactions largely overlapped with those of keratin 14 (K14), a marker of basal cells, in the airway epithelium, and they partially overlapped with those of K14 in the olfactory epithelium. Ca2+ imaging analysis revealed that hypo-osmotic stimulation and 4α-phorbol 12,13 didecanoate (4α-PDD), both of which are TRPV4 agonists, caused an increase in the cytosolic Ca2+ concentration in a subset of primary epithelial cells cultured from the upper parts of the nasal epithelium of the wild-type mice. This response was barely noticeable in cells from similar parts of the epithelium in TRPV4-KO mice. Finally, there was no significant difference in BrdU-labeled proliferation between the olfactory epithelia of wild-type and TRPV4-KO mice under normal conditions. Thus, TRPV4 channels are functionally expressed in basal cells throughout the nasal epithelium and may act as sensors for the development and injury-induced regeneration of basal stem cells.

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Effects of adenoviral vector-mediated BDNF expression on the bulbectomy-induced apoptosis of olfactory receptor neurons

Cited by 11 publications

References 23 publications

The proto‐oncogene BCL6 promotes survival of olfactory sensory neurons

The proto‐oncogene BCL6 promotes survival of olfactory sensory neurons

Chitosan films promote formation of olfactory neurospheres and differentiation of olfactory receptor neurons

Basal cells express functional TRPV4 channels in the mouse nasal epithelium

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