Isoyama Kyoko, Nagata Hiroshi, Shino Yuji, Isegawa Naohisa, Arimoto Yukiko, Koda Masao, Kumahara Keiichiro, Okamoto Yoshitaka, Shirasawa Hiroshi
Department of Otorhinolaryngology (J2), Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chiba 260-8670, Japan.
Brain Res Mol Brain Res. 2004 Oct 22;129(1-2):88-95. doi: 10.1016/j.molbrainres.2004.06.031.
The expression of adenoviral vector (Ad)-mediated lacZ and brain-derived neurotrophic factor (BDNF) in mouse olfactory epithelium (OE) was examined, and the effect of BDNF on the survival of the bulbectomized OE was evaluated. A recombinant adenovirus, Ax1CAlacZ, was administrated into the mouse OE after bulbectomy, and the expression of a transferred E. coli beta-galactosidase (beta-gal) gene was confirmed by X-gal staining. The expression and effects of exogenous BDNF in the OE after bulbectomy were examined using immunohistochemistry and the TUNEL method. The adenoviral vector-mediated expression of beta-gal in the mouse OE was detectable for up to 14 days after bulbectomy in vivo. The Ad-mediated expression of BDNF was also observed in the OE after bulbectomy. Exogenously induced BDNF suppressed the degenerative changes of bulbectomized OE. TUNEL staining indicated that the exogenous BDNF enhanced the survival of the bulbectomized OE by inhibiting apoptosis. Ad-mediated expression of BDNF in the mouse nasal mucosa alleviated degenerative changes in bulbectomized OE. Ad-mediated transfer of neurotrophic factors might be applicable in the treatment of olfactory disorders.
检测了腺病毒载体（Ad）介导的β-半乳糖苷酶（lacZ）和脑源性神经营养因子（BDNF）在小鼠嗅上皮（OE）中的表达，并评估了BDNF对切除嗅球的OE存活的影响。在切除嗅球后，将重组腺病毒Ax1CAlacZ注入小鼠OE，通过X-gal染色确认转移的大肠杆菌β-半乳糖苷酶（β-gal）基因的表达。使用免疫组织化学和TUNEL法检测切除嗅球后OE中外源性BDNF的表达和作用。在体内切除嗅球后长达14天可检测到腺病毒载体介导的β-gal在小鼠OE中的表达。在切除嗅球后的OE中也观察到Ad介导的BDNF表达。外源性诱导的BDNF抑制了切除嗅球的OE的退行性变化。TUNEL染色表明，外源性BDNF通过抑制细胞凋亡提高了切除嗅球的OE的存活率。Ad介导的BDNF在小鼠鼻粘膜中的表达减轻了切除嗅球的OE的退行性变化。Ad介导的神经营养因子转移可能适用于嗅觉障碍的治疗。
