Journal of Applied Genetics

, Volume 60, Issue 3–4, pp 357–365 | Cite as

Decreased neural stem cell proliferation and olfaction in mouse models of Niemann–Pick C1 disease and the response to hydroxypropyl-β-cyclodextrin

  • Jessica Dragotto
  • Giampiero Palladino
  • Sonia Canterini
  • Paola Caporali
  • Rutaraj Patil
  • Maria Teresa Fiorenza
  • Robert P. EricksonEmail author
Human Genetics • Original Paper


The Npc1nih/nih-null model and the Npc1nmf164/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, Npc1nih/nih homozygous mice showed a highly significant delay in finding the food compared with wild-type mice. Npc1nmf164/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 Npc1nmf164/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.


Olfaction Niemann–Pick C1 disease Hydroxypropyl-beta-cyclodextrins Neural stem cells Nasal delivery 





Niemann–Pick C


Olfactory bulb


Subventricular zone



RPE acknowledges the support of the University Roma, La Sapienza for visiting research professorships.

Authors’ contributions

J. D. and G. P. performed BrdU labelling, immunohistochemistry, and treatments; G. P. and P. C. performed olfactory testing; S. C. performed HPBCD treatments and supervised experiments; M. T. F. and R. P. E. conceived the study and wrote the manuscript.

Funding information

The financial supports of Telethon Foundation - Italy (grant no. GGP13183 to M.T.F.) and the Ateneo La Sapienza (RM11615501ED6577) are gratefully acknowledged.

Compliance with ethical standards

Experimental protocols and related procedures were approved by the University of Arizona IACUC Institutional Animal Care Utilization Committee and Italian Ministry of Public Health. All experiments were conducted according to the Italia law DL 26/2014 on the protection of animals used for scientific purpose.

Conflict of interest

The authors declare that they have no competing interests.


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Copyright information

© Institute of Plant Genetics, Polish Academy of Sciences, Poznan 2019

Authors and Affiliations

  1. 1.Division of Neuroscience, Department of PsychologyUniversità La Sapienza di RomaRomeItaly
  2. 2.Department of PediatricsUniversity of Arizona School of MedicineTucsonUSA
  3. 3.IRCCS Fondazione Santa LuciaRomeItaly

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