当前位置： SCI文献检索 > NEUROSCIENCE期刊下所有文献 > Combined therapy with cyclodextrin/allopregnanolone and miglustat improves motor but not cognitive functions in Niemann-Pick Type C1 mice.

Combined therapy with cyclodextrin/allopregnanolone and miglustat improves motor but not cognitive functions in Niemann-Pick Type C1 mice.

Abstract：

:Niemann-Pick Type C1 (NPC1) is an autosomal recessive disorder characterized by the accumulation of cholesterol and glycosphingolipids. Combination-treatment utilizing cyclodextrin, allopregnanolone and miglustat (CYCLO/ALLO/miglustat) can ameliorate NPC1 disease in a mutant mouse model. The present study was designed to add behavioral analysis in NPC1 mutant mice upon CYCLO/ALLO/miglustat therapy. NPC1 mutant (BALB/cJ NPC1NIH) and control mice were used. For the combination treatment mice were injected with CYCLO/ALLO weekly, starting at P7. The miglustat injection was performed daily from P10 till P23. Starting at P23, miglustat was added to the powdered chow. For the sham treatment of control and mutant mice the same schedule was used with 0.9% NaCl injection. Locomotor activity was assessed in open field, elevated plus maze and accelerod tests. For assessment of spatial learning and memory the Morris water maze test was conducted. Electron microscopy has been performed to support the behavioral data. The sham-treated mutant mice exhibited motor impairments in all performed tests. In the water maze the sham-treated mutants exhibited impairment in remembering the location of the hidden platform. CYCLO/ALLO/miglustat treatment positively influenced motor dysfunction: total distance and number of visits significantly increased, and accelerod performance improved. The spatial learning, however, did not benefit from therapy. At the morphological level, an excessive accumulation of electron-dense material was seen in the cerebellar Purkinje cells of mutant mice. A regression of these autophagosomal inclusions was seen upon therapy. CYCLO/ALLO/miglustat therapy ameliorates motor but not cognitive deficits in NPC1 mutant mice, suggesting unequal vulnerability of different brain areas to the treatment.

journal_name

Neuroscience

journal_title

Neuroscience

authors

Hovakimyan M,Maass F,Petersen J,Holzmann C,Witt M,Lukas J,Frech MJ,Hübner R,Rolfs A,Wree A

doi

10.1016/j.neuroscience.2013.08.001

subject

Has Abstract

pub_date

2013-11-12 00:00:00

pages

201-11

eissn

0306-4522

issn

1873-7544

pii

S0306-4522(13)00679-9

journal_volume

252

pub_type

杂志文章

相关文献

NEUROSCIENCE文献大全