Abstract：
OBJECTIVE: Periglomerular and granule cells in the adult mammalian olfactory bulb modulate olfactory signal transmission. These cells originate from the subventricular zone, migrate to the olfactory bulb via the Rostral Migratory Stream (RMS), and differentiate into mature cells within the olfactory bulb throughout postnatal life. While the regulation of neuroblast development is known to be affected by external stimuli, there is a lack of information concerning changes that occur during the recovery process after injury caused by external stimuli. To address this gap in research, the present study conducted histological observations to investigate changes in the olfactory bulb and RMS occurring after the degeneration and regeneration of olfactory neurons.
METHODS: To create a model of olfactory neurodegeneration, adult mice were administered methimazole intraperitoneally. Nasal tissue and whole brains were removed 3, 7, 14 and 28 days after methimazole administration, and EdU was administered 2 and 4 h before removal of these tissues to monitor dividing cells in the RMS. Methimazole-untreated mice were used as controls. Olfactory nerve fibers entering the olfactory glomerulus were observed immunohistochemically using anti-olfactory marker protein. In the brain tissue, the entire RMS was observed and the volume and total number of cells in the RMS were measured. In addition, the number of neuroblasts and dividing neuroblasts passing through the RMS were measured using anti-doublecortin and anti-EdU antibodies, respectively. Statistical analysis was performed using the Tukey test.
RESULTS: Olfactory epithelium degenerated was observed after methimazole administration, and recovered after 28 days. In the olfactory glomeruli, degeneration of OMP fibers began after methimazole administration, and after day 14, OMP fibers were reduced or absent by day 28, and overall OMP positive fibers were less than 20%. Glomerular volume tended to decrease after methimazole administration and did not appear to recover, even 28 days after recovery of the olfactory epithelium. In the RMS, EdU-positive cells decreased on day 3 and began to increase on day 7. However, they did not recover to the same levels as the control methimazole-untreated mice even after 28 days.
CONCLUSIONS: These results suggest that the division and maturation of neuroblasts migrating from the RMS was suppressed by olfactory nerve degeneration or the disruption of olfactory input.
METHODS: To create a model of olfactory neurodegeneration, adult mice were administered methimazole intraperitoneally. Nasal tissue and whole brains were removed 3, 7, 14 and 28 days after methimazole administration, and EdU was administered 2 and 4 h before removal of these tissues to monitor dividing cells in the RMS. Methimazole-untreated mice were used as controls. Olfactory nerve fibers entering the olfactory glomerulus were observed immunohistochemically using anti-olfactory marker protein. In the brain tissue, the entire RMS was observed and the volume and total number of cells in the RMS were measured. In addition, the number of neuroblasts and dividing neuroblasts passing through the RMS were measured using anti-doublecortin and anti-EdU antibodies, respectively. Statistical analysis was performed using the Tukey test.
RESULTS: Olfactory epithelium degenerated was observed after methimazole administration, and recovered after 28 days. In the olfactory glomeruli, degeneration of OMP fibers began after methimazole administration, and after day 14, OMP fibers were reduced or absent by day 28, and overall OMP positive fibers were less than 20%. Glomerular volume tended to decrease after methimazole administration and did not appear to recover, even 28 days after recovery of the olfactory epithelium. In the RMS, EdU-positive cells decreased on day 3 and began to increase on day 7. However, they did not recover to the same levels as the control methimazole-untreated mice even after 28 days.
CONCLUSIONS: These results suggest that the division and maturation of neuroblasts migrating from the RMS was suppressed by olfactory nerve degeneration or the disruption of olfactory input.
摘要：
目的：成年哺乳动物嗅球中的肾小球和颗粒细胞调节嗅觉信号的传递。这些细胞来自脑室下区,通过词尾迁移流(RMS)迁移到嗅球，并在出生后的整个生命中分化为嗅球内的成熟细胞。虽然已知神经母细胞发育的调节受到外部刺激的影响，缺乏有关外部刺激引起的损伤后恢复过程中发生的变化的信息。为了解决研究中的这一差距，本研究进行了组织学观察，以研究嗅觉神经元变性和再生后发生的嗅球和RMS的变化。
方法：为了建立嗅觉神经变性模型，成年小鼠腹腔内给予甲氧咪唑。给药后3、7、14和28天取鼻组织和全脑,在去除这些组织之前2和4小时施用EdU以监测RMS中的分裂细胞。使用未处理的甲咪唑小鼠作为对照。使用抗嗅觉标记蛋白免疫组织化学观察进入嗅觉肾小球的嗅觉神经纤维。在脑组织中，观察整个RMS,并测量RMS中细胞的体积和总数。此外,使用抗双皮质素和抗EdU抗体测量通过RMS的成神经细胞和分裂成神经细胞的数量，分别。使用Tukey检验进行统计分析。
结果：甲氧咪唑给药后观察到嗅觉上皮变性，28天后康复。在嗅觉肾小球中，OMP纤维的变性在甲氧咪唑给药后开始，在第14天之后,到第28天,OMP纤维减少或不存在,并且总体OMP阳性纤维小于20%。在甲氧咪唑给药后，肾小球体积趋于减少，并且似乎没有恢复，甚至28天后恢复嗅觉上皮。在RMS中,EdU阳性细胞在第3天减少,并在第7天开始增加。然而,即使在28天后，它们也没有恢复到与未治疗的对照组小鼠相同的水平。
结论：这些结果表明，从RMS迁移的成神经细胞的分裂和成熟受到嗅觉神经变性或嗅觉输入中断的抑制。
方法：为了建立嗅觉神经变性模型，成年小鼠腹腔内给予甲氧咪唑。给药后3、7、14和28天取鼻组织和全脑,在去除这些组织之前2和4小时施用EdU以监测RMS中的分裂细胞。使用未处理的甲咪唑小鼠作为对照。使用抗嗅觉标记蛋白免疫组织化学观察进入嗅觉肾小球的嗅觉神经纤维。在脑组织中，观察整个RMS,并测量RMS中细胞的体积和总数。此外,使用抗双皮质素和抗EdU抗体测量通过RMS的成神经细胞和分裂成神经细胞的数量，分别。使用Tukey检验进行统计分析。
结果：甲氧咪唑给药后观察到嗅觉上皮变性，28天后康复。在嗅觉肾小球中，OMP纤维的变性在甲氧咪唑给药后开始，在第14天之后,到第28天,OMP纤维减少或不存在,并且总体OMP阳性纤维小于20%。在甲氧咪唑给药后，肾小球体积趋于减少，并且似乎没有恢复，甚至28天后恢复嗅觉上皮。在RMS中,EdU阳性细胞在第3天减少,并在第7天开始增加。然而,即使在28天后，它们也没有恢复到与未治疗的对照组小鼠相同的水平。
结论：这些结果表明，从RMS迁移的成神经细胞的分裂和成熟受到嗅觉神经变性或嗅觉输入中断的抑制。
