The Npc1^nih/nih-null model and the Npc1^{nmf164/nmf164} hypomorph models of Niemann–Pick C1 (NPC1) disease show defects in olfaction. We have tested the effects of the life-prolonging treatment hydroxypropyl-beta-cyclodextrin (HPBCD) on olfaction and neural stem cell numbers when delivered either systemically or by nasal inhalation. Using the paradigm of finding a hidden cube of food after overnight food deprivation, Npc1^nih/nih homozygous mice showed a highly significant delay in finding the food compared with wild-type mice. Npc1^{nmf164/nmf164} homozygous mice showed an early loss of olfaction which was mildly corrected by somatic delivery of HPBCD which also increased the number of neural stem cells in the mutant but did not change the number in wild-type mice. In contrast, nasal delivery of this drug, at 1/5 the dosage used for somatic delivery, to Npc1^{nmf164/nmf164} mutant mice delayed loss of olfaction but the control of nasal delivered saline did so as well. The nasal delivery of HPBCD to wild-type mice caused loss of olfaction but nasal delivery of saline did not. Neural stem cell counts were not improved by nasal therapy with HPBCD. We credit the delay in olfaction found with the treatment, a delay which was also found for time of death, to a large amount of stimulation the mice received with handling during the nasal delivery.

中文翻译：

---

在Niemann-Pick C1病小鼠模型中神经干细胞增殖和嗅觉降低以及对羟丙基-β-环糊精的反应降低。

该NPC1 ^{NIH / NIH} -空模型和NPC1 ^{nmf164 / nmf164}的hypomorph模型尼曼-匹克C1（NPC1）疾病秀缺陷嗅觉。我们已经测试了延长寿命的治疗羟丙基-β-环糊精（HPBCD）对嗅觉和神经干细胞数量的影响，无论是全身给药还是通过鼻吸入给药。Npc1 nih ^/ nih纯合小鼠使用一种在过夜禁食后发现隐藏的食物立方体的范例，与野生型小鼠相比，发现食物的延迟显着增加。NPC1 ^{nmf164 / nmf164}纯合小鼠表现出嗅觉的早期丧失，其通过体细胞递送HPBCD得到了轻度的纠正，这也增加了突变体中神经干细胞的数量，但没有改变野生型小鼠的数量。相比之下，以NPC1 ^{nmf164 / nmf164}突变小鼠的体细胞给药剂量的1/5鼻腔给药延迟了嗅觉丧失，但鼻腔给药盐水的控制也是如此。HPBCD鼻腔输送至野生型小鼠引起嗅觉丧失，而盐水鼻腔输送并未引起嗅觉丧失。通过HPBCD鼻腔治疗无法改善神经干细胞计数。我们将这种治疗中嗅觉的延迟归因于老鼠在鼻腔输送过程中接受的大量刺激，这种延迟也是在死亡时间上发现的。