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Int J Mol Sci. 2016 Nov 9;17(11). pii: E1866.

Pharmacologic Treatment Assigned for Niemann Pick Type C1 Disease Partly Changes Behavioral Traits in Wild-Type Mice.

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Institute of Anatomy, University of Rostock, 18055 Rostock, Germany.
Institute of Anatomy, University of Rostock, 18055 Rostock, Germany.
Institute of Medical Genetics, Rostock University Medical Center, 18057 Rostock, Germany.
Institute of Anatomy, University of Rostock, 18055 Rostock, Germany.
Department for Biostatistics and Clinical Epidemiology, Charité-Universitätsmedizin Berlin, 10117 Berlin, Germany.
Albrecht-Kossel Institute for Neuroregeneration, Rostock University Medical Center, 18147 Rostock, Germany.
Institute of Anatomy, University of Rostock, 18055 Rostock, Germany.


Niemann-Pick Type C1 (NPC1) is an autosomal recessive inherited disorder characterized by accumulation of cholesterol and glycosphingolipids. Previously, we demonstrated that BALB/c-npc1nihNpc1-/- mice treated with miglustat, cyclodextrin and allopregnanolone generally performed better than untreated Npc1-/- animals. Unexpectedly, they also seemed to accomplish motor tests better than their sham-treated wild-type littermates. However, combination-treated mutant mice displayed worse cognition performance compared to sham-treated ones. To evaluate effects of these drugs in healthy BALB/c mice, we here analyzed pharmacologic effects on motor and cognitive behavior of wild-type mice. For combination treatment mice were injected with allopregnanolone/cyclodextrin weekly, starting at P7. Miglustat injections were performed daily from P10 till P23. Starting at P23, miglustat was embedded in the chow. Other mice were treated with miglustat only, or sham-treated. The battery of behavioral tests consisted of accelerod, Morris water maze, elevated plus maze, open field and hot-plate tests. Motor capabilities and spontaneous motor behavior were unaltered in both drug-treated groups. Miglustat-treated wild-type mice displayed impaired spatial learning compared to sham- and combination-treated mice. Both combination- and miglustat-treated mice showed enhanced anxiety in the elevated plus maze compared to sham-treated mice. Additionally, combination treatment as well as miglustat alone significantly reduced brain weight, whereas only combination treatment reduced body weight significantly. Our results suggest that allopregnanolone/cyclodextrin ameliorate most side effects of miglustat in wild-type mice.


Morris water maze; NPC; accelerod; allopregnanolone; behavior; cyclodextrin; elevated plus maze; hot-plate; mice; miglustat; open field

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