Regeneration of olfactory neuroepithelium in 3-methylindole-induced anosmic rats treated with intranasal chitosan
Journal
Biomaterials
Journal Volume
271
Date Issued
2021
Author(s)
Abstract
Olfactory dysfunction significantly impairs the life quality of patients but without effective treatments to date. The previous report has demonstrated that chitosan mediates the differentiation of olfactory receptor neurons (ORNs) through insulin-like growth factors and insulin-like growth factor binding protein-2 axis in an in vitro model. However, whether chitosan can further treat olfactory dysfunction in vivo remains unexplored. This study aims to evaluate the therapeutic effect of chitosan on a 3-methylindole-induced anosmic rat model. Intraperitoneal injection of 3-methylindole is performed to induce anosmia in rats. Experimental results demonstrate that the food-finding duration after chitosan treatment gradually decrease to around 80 s, and both the olfactory neuroepithelium (ON) thickness and mature ORNs (expressing olfactory marker protein) are significantly restored. Furthermore, proliferating cells (expressing bromodeoxyuridine) are mainly co-expressed with immature ORNs (expressing βIII tubulin) below the intermediate layer of the ON in the chitosan-treated group on day 28 following 3-methylindole treatment. Conversely, proliferating cells are scattered over the ON, and co-localized with immature ORNs and sustentacular cells (expressing keratin 18) in the sham group, and even immature ORNs go into apoptosis (expressing DNA fragmentation and cleaved caspase-3), possibly causing incomplete regeneration. Consequently, chitosan regenerates the ON by regulating olfactory neural homeostasis and reducing ORN apoptosis, and serves as a potential therapeutic intervention for olfactory dysfunction in the future. ? 2021 Elsevier Ltd
Subjects
Anosmia
Apoptosis
Chitosan
Olfactory dysfunction
Olfactory neural homeostasis
Olfactory receptor neurons
Sustentacular cells
Cell culture
Cell proliferation
Insulin
Neurons
Patient treatment
Proteins
Rats
Insulin-like growth factor
Intranasal
Life qualities
Olfactory receptor neuron
Olfactory receptors
Proliferating cells
Sustentacular cell
Cell death
beta tubulin
broxuridine
caspase 3
chitosan
cytokeratin 18
olfactory marker protein
skatole
animal cell
animal experiment
animal model
animal tissue
anosmia
Article
cell fate
cell maturation
cell proliferation
cellular distribution
controlled study
DNA fragmentation
drug effect
food-seeking behavior
male
nerve cell growth
nerve regeneration
neuroapoptosis
neuroepithelium
nonhuman
olfactory receptor neuron
priority journal
protein cleavage
protein expression
rat
rat model
Sprague Dawley rat
sustentacular cell
thickness
treatment duration
animal
cell differentiation
human
olfactory mucosa
regeneration
Animals
Cell Differentiation
Humans
Olfactory Mucosa
Olfactory Receptor Neurons
Regeneration
Skatole
SDGs
Type
journal article