The effects of hydroxypropyl-beta-cyclodextrin on olfaction in mouse models of Niemann-Pick C1 Disease
AffiliationUniv Arizona, Sch Med, Dept Pediat
Niemann-Pick C1 disease
Neural stem cells
MetadataShow full item record
CitationJ. Applied Genet. 60:357-365.
JournalJOURNAL OF APPLIED GENETICS
Rights© Institute of Plant Genetics, Polish Academy of Sciences, Poznan 2019.
Collection InformationThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at email@example.com.
AbstractThe 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.
Note12 month embargo; first Online: 04 September 2019
VersionFinal accepted manuscript
SponsorsTelethon Foundation - Italy, Fondazione Telethon [GGP13183]; Ateneo La Sapienza, Sapienza University Rome [RM11615501ED6577]
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