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衰老的嗅觉上皮:神经发生、对损伤的反应及气味诱导的活动。

The aging olfactory epithelium: neurogenesis, response to damage, and odorant-induced activity.

作者信息

Loo A T, Youngentob S L, Kent P F, Schwob J E

机构信息

Department of Physiology, SUNY Health Science Center 13210, USA.

出版信息

Int J Dev Neurosci. 1996 Nov;14(7-8):881-900. doi: 10.1016/s0736-5748(96)00046-9.

DOI:10.1016/s0736-5748(96)00046-9
PMID:9010732
Abstract

Olfactory epithelium retains the capacity to recover anatomically after damage well into adult life and perhaps throughout its duration. None the less, olfactory dysfunctions have been reported widely for elderly humans. The present study investigates the effects of aging on the neurophysiological and anatomical status of the olfactory epithelium in barrier-raised Fischer 344X Brown Norway F1 hybrid rats at 7, 10, 25 and 32/35 months old. The posterior part of the olfactory epithelium in 32/35-month-old rats is well preserved. Globose basal cells are dividing, and new neurons are being born even at this advanced age. None the less, the numbers of proliferating basal cells and immature, GAP-43 (+) neurons are significantly decreased. Neurophysiological status was evaluated using voltage-sensitive dye techniques to assess inherent patterns of odorant-induced activity in the epithelium lining the septum and the medial surface of the turbinates. In middle and posterior zones of the epithelium, there were neither age-related changes in overall responsivity of this part of the olfactory epithelium to any of five odorants, nor shifts in the location of the odorant-induced hotspots. The inherent activity patterns elicited by the different odorants do become more distinct as a function of age, which probably reflects the decline in immature neurons and a slight, but not statistically significant, increase in mature neurons as a function of age. In contrast with the excellent preservation of posterior epithelium, the epithelium lining the anterodorsal septum and the corresponding face of the turbinates is damaged in the 32/35-month-old animals: in this part, horizontal basal cells are reactive, more basal cells and sustentacular cells are proliferating than in younger animals or in posterior epithelium of the same animals, and the neuronal population is less mature on average. Our findings indicate that degeneration of the olfactory epithelium is not an inevitable or pre-programmed consequence of the aging process, since the posterior zone of the epithelium is very well preserved in these barrier-protected animals. However, the deterioration in the anterior epithelium suggests that environmental insults can accumulate or become more severe with age and overwhelm the regenerative capacity of the epithelium. Alternatively, the regenerative capacity of the epithelium may wane somewhat with age. Either of these mechanisms or some combination of them can account for the functional and anatomical deterioration of the sense of smell associated with senescence in humans.

摘要

嗅觉上皮在成年后甚至可能在其整个生命周期内都保留着受损后进行解剖学恢复的能力。尽管如此,老年人类中嗅觉功能障碍的报道却很广泛。本研究调查了衰老对屏障饲养的7、10、25和32/35月龄Fischer 344X Brown Norway F1杂交大鼠嗅觉上皮神经生理和解剖状态的影响。32/35月龄大鼠的嗅觉上皮后部保存完好。球状基底细胞正在分裂,即使在这个高龄阶段也有新的神经元产生。尽管如此,增殖的基底细胞和未成熟的、GAP - 43(+)神经元的数量显著减少。使用电压敏感染料技术评估神经生理状态,以评估鼻中隔和鼻甲内侧表面上皮中气味诱导活动的固有模式。在上皮的中后区域,嗅觉上皮的这一部分对五种气味中的任何一种的总体反应性均未出现与年龄相关的变化,气味诱导热点的位置也没有偏移。不同气味引发的固有活动模式确实会随着年龄的增长而变得更加明显,这可能反映了未成熟神经元数量的减少以及成熟神经元数量随年龄增长略有增加,但在统计学上不显著。与后部上皮的良好保存形成对比的是,32/35月龄动物的前背鼻中隔和鼻甲相应面的上皮受到了损伤:在这部分,水平基底细胞有反应,与年轻动物或同一动物的后部上皮相比,更多的基底细胞和支持细胞在增殖,并且神经元群体平均成熟度较低。我们的研究结果表明,嗅觉上皮的退化并非衰老过程中不可避免或预先设定的结果,因为在这些受到屏障保护的动物中,上皮的后部区域保存得非常好。然而,前部上皮的恶化表明,随着年龄的增长,环境损伤可能会积累或变得更加严重,从而超过上皮的再生能力。或者,上皮的再生能力可能会随着年龄的增长而有所下降。这些机制中的任何一种或它们的某种组合都可以解释与人类衰老相关的嗅觉功能和解剖结构的退化。

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