Allopregnanolone treatment, both as a single injection or repetitively, delays demyelination and enhances survival of Niemann-Pick C mice

Iram Ahmad, Silvia Lope-Piedrafita, Xiaoning Bi, Chad Hicks, Yueqin Yao, Clara Yu, Elizabeth Chaitkin, Christine M. Howison, Lyndon Weberg, Theodore P. Trouard, Robert P. Erickson

Research output: Contribution to journalArticlepeer-review

75 Scopus citations


Niemann-Pick C disease (NPC) is an irreversible neurodegenerative disorder without current treatment. It is thought to result from deficient intracellular cholesterol and/or ganglioside trafficking. We have investigated the effects of allopregnanolone treatments on survival, weight loss, motor function, magnetic resonance imaging (MRI), and neuropathology in the mouse model of NPC (Npc1 -/- mice). We confirmed previous results showing that a single injection of 250 μg of allopregnanolone on postnatal day 7 significantly extended the life span of Npc1-/- mice. This caused a marked difference in the weight curves of the treated mice but no statistical difference in the Rota-Rod performance. T2-weighted MRI and diffusion tensor imaging (DTI) of treated mice showed values of signal intensity and fractional anisotropy closer to those of wild-type mice than those of untreated Npc1 -/- mice. Neuropathology showed that day-7 treatment markedly suppressed astrocyte reaction and significantly reduced microglial activation. Furthermore, the steroid treatment also increased myelination in brains of Npc1-/- mice. Similar effects of allopregnanolone treatment were observed in Npc1-/-, mdr1a-/- double-mutant mice, which have a deficient blood-brain barrier, resulting in increased steroid uptake. The effects on survival and weight loss of a single injection on day 7 followed by injections every 2 weeks were also evaluated in Npc1-/- mice, and the beneficial effects were found to be greater than with the single injection at day 7. We conclude that allopregnanolone treatment significantly ameliorates several symptoms of NPC in Npc1-/- mice, presumably by effects on myelination or neuronal connectivity.

Original languageEnglish (US)
Pages (from-to)811-821
Number of pages11
JournalJournal of Neuroscience Research
Issue number6
StatePublished - Dec 15 2005


  • Magnetic resonance imaging
  • Mouse models
  • Neurodegeneration
  • Neurosteroids
  • Niemann-Pick C

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience


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