RESUMO
In the mammalian olfactory epithelium (OE), neurogenesis continues throughout the lifetime, by replacing olfactory receptor neurons (ORNs) lost by normal turnover in the postnatal period. However, this ability decreases with age and/or because of various toxic factors. To date, no effective treatment for olfactory dysfunction' especially because of aging, is available in clinical practice. Here, we examined the effects of intranasal administration of fibroblast growth factor-2 and insulin-like growth factor-1 in gelatin hydrogel on the degenerated OE of aging mice induced by methimazole administration. These topical treatments led to increases in the number of olfactory marker protein-positive cells, which identified mature ORNs, resulting in the increased thickness of OE. These results indicate that both fibroblast growth factor-2 and insulin-like growth factor-1 promote the proliferation of basal cells and differentiation of immature ORNs into mature ORNs in the degenerated OE of aging mice. These agents might be promising candidates for the treatment of degenerated OE of aging humans.
Assuntos
Fator 2 de Crescimento de Fibroblastos/administração & dosagem , Fator de Crescimento Insulin-Like I/administração & dosagem , Degeneração Neural/tratamento farmacológico , Mucosa Olfatória/patologia , Regeneração/efeitos dos fármacos , Administração Intranasal , Envelhecimento , Animais , Proteína GAP-43/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Camundongos , Degeneração Neural/induzido quimicamente , Proteína de Marcador Olfatório/metabolismoRESUMO
To further understand the roles of growth factors in the olfactory neurogenesis, we studied the mRNA levels of diverse genes in olfactory bulb (OB) and olfactory epithelium (OE) during the regeneration process of OE. mRNA expression levels of various genes in the OB and OE during the regeneration processes of OE from damage induced by methimazole administration were studied by DNA microarray analysis. The results were confirmed by quantitative real-time RT-PCR and immunohistochemistry. Expression levels of various genes dramatically changed during the observation period. Among them, mRNA expression of BDNF dramatically increased in OE during the first 7 days and then decreased. In contrast, mRNA expression of BDNF in OB significantly decreased during the first 7 days after administration and then gradually increased. The changes in the mRNA levels of OMP in OB precisely followed those of OMP in OE and OB. The present results suggest that BDNF in OE contributes to the early stage of regeneration, and BDNF in OB has its role in the late stage of regeneration of olfactory receptor neurons (ORNs).