Recovery following peripheral destruction of olfactory neurons in young and adult mice

Abstract

Olfactory neurons (ON) which are located in the olfactory epithelium are responsible of odorous molecule detection. A unique feature of these cells is their continuous replacement throughout life due to the proliferation and differentiation of local neural precursors, the basal cells. Thus, experimental destruction of all ON induces a stimulation of basal cell division followed by tissue regeneration. The fact that ON precursors display such proliferative and neurogenic activity in adults makes these cells particularly attractive as a potential tool for nervous system repair. However, basal cell proliferation and, thus, ON production, decrease in relation to age; mostly during the first months of life. Therefore, we aimed to seek whether the ability of ON precursors to yield new functional ON in regenerative conditions was consequently impaired in adult. ZnSO4 intranasal perfusion administered to young (1 month) and adult (6 months) mice leads in a few days to total ON destruction and to hyposmia. Tissue and function restoration occurred in the following weeks in both mice groups and was preceded by a transient peak of cell division. In adults, although neurogenesis in the impaired olfactory epithelium was less efficient than in young mice, neural precursors retain their ability to provide new functional ON as indicated by the butanol detection recovery. This was achieved more rapidly than total ON regeneration, suggesting that a reduced number of reconnected ON may be sufficient for odor discrimination.

Response of olfactory ensheathing cells to the degeneration and regeneration of the peripheral olfactory system and the involvement of the neuregulins

“…This can be achieved by irrigating the nasal cavity with a ZnSO 4 solution, causing widespread death of ORNs and triggering the simultaneous generation of new ORNs and their axons. Our description of the time course of degenerative events is broadly similar to the time courses reported in earlier studies after ZnSO 4 treatment (Cancalon, 1982;Burd, 1993;Chuah et al, 1995;Ducray et al, 2002) and methyl bromide inhalation (Schwob et al, 1995(Schwob et al, , 1999; however, we have extended the time frame of the analysis, examining simultaneous antigenic changes and correlating these with the inflammatory and proliferative responses throughout the olfactory system. We found that degeneration of the olfac- Fig.…”

Neurotoxic, Inflammatory, and Mucosecretory Responses in the Nasal Airways of Mice Repeatedly Exposed to the Macrocyclic Trichothecene Mycotoxin Roridin A

“…Loss of OSNs Intranasal perfusion with ZnSO 4 has been used to induce OSN death in mice and rats to study recovery of OSNs following chemical lesion (Burd 1993;Herzog and Otto 1999). Ducray et al (2002) showed that mice could differentiate water and butanol in a behavioral test maze approximately 18 days following intranasal instillation of ZnSO 4 , indicating that an intact sense of smell was present. In that study, OMP staining was significantly reduced at 25 and 35 days after instillation in treated mice in spite of the recovery of olfactory-mediated behavior at 18 days.…”

Distribution and severity of spontaneous lesions in the neuroepithelium and Bowman’s glands in mouse olfactory mucosa: age-related progression

“…Several previous studies have demonstrated that the extent of epithelial damage in olfactory mucosa and the increase in the threshold of olfactory perception in the same animal are not proportional, with only a small population of mature ORNs (<5% of the normal population) remaining or regenerating after experimental injury seeming to be sufficient to maintain the ability to detect odors (Ducray et al 2002;Youngentob et al 1997). This finding suggests that the peripheral olfactory system has a high level of spare ability, enabling the individual to maintain olfactory perception even when the olfactory mucosa is being damaged.…”

“…Clinically, olfactory disorder after upper respiratory viral infection, which is caused by the degeneration of the olfactory mucosa (Bihun and Percy 1995;Moran et al 1992;Yamagishi et al 1994), mainly occurs in the elderly population, with functional recovery tending to become increasingly incomplete with advancing age of the patient (Reden et al 2006;Temmel et al 2002). Anatomical recovery of olfactory neuroepithelium after experimental destruction also tends to be less complete with increasing age (Ducray et al 2002). These findings suggest that aged olfactory mucosa is more vulnerable to extrinsic insults and has a reduced capacity to restore normal structure and function following damage.…”