Progressive neuronal loss in the ventral posterior lateral and medial nuclei of thalamus in Niemann-Pick disease type C mouse brain

被引：50

作者：

Yamada, A ^{[1
]}

Saji, M ^{[1
]}

Ukita, Y ^{[1
]}

Shinoda, Y ^{[1
]}

Taniguchi, M ^{[1
]}

Higaki, K ^{[1
]}

Ninomiya, H ^{[1
]}

Ohno, K ^{[1
]}

机构：

[1] Tottori Univ, Sch Life Sci, Dept Neurobiol, Fac Med, Yonago, Tottori 6838503, Japan

来源：

BRAIN & DEVELOPMENT | 2001年 / 23卷 / 05期

关键词：

Niemann-Pick disease type C; neuronal cell loss; Purkinje cell; thalamus; cholesterol; filipin;

D O I：

10.1016/S0387-7604(01)00209-1

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Niemann-Pick disease type C (NP-C) disease is a progressive and fatal neurological disorder characterized by accumulation of cholesterol and glycosphingolipids in peripheral tissues and that of glycosphingolipids in the brain. A C57BL/KsJ-npc1(spm) mutant strain is a genetically authentic model of NP-C. This study investigated neuronal cell loss and lipid accumulation in the npc1(spm) mouse brain. Nissl-staining revealed abundant swollen neurons in the neocortex, piriform cortex, hippocampus and basal ganglia at 3-4 wk of age. In addition to loss of the Purkinje cells, we found a conspicuous cell loss in the ventral posterial lateral (VPL) and medial (VPM) nuclei of thalamus, which became apparent after 4-5 wk. Biochemical analyses revealed no increase of cholesterol in the lipid extracts whereas a substantial accumulation of cholesterol was detectable in most of the large neurons by filipin staining in the brain of homozygous mice. In contrast to the diffuse staining pattern in normal brains, the neuropils of the neurons in the brain of homozygous mice were stained in a punctate pattern. The ubiquitous accumulation excludes a direct role of cholesterol in the progressive neuronal loss in the Purkinje cell layer and in the VPL and VPM of the thalamus. (C) 2001 Elsevier Science B.V. All rights reserved.

引用

页码：288 / 297

页数：10

共 39 条

[1] A C57BL/KsJ mouse model of Niemann-Pick disease (spm) belongs to the same complementation group as the major childhood type of Niemann-Pick disease type C [J].

Akaboshi, S ;

Yano, T ;

Miyawaki, S ;

Ohno, K ;

Takeshita, K .

HUMAN GENETICS, 1997, 99 (03) :350-353

[2]

BROWN DE, 1994, AM J PATHOL, V144, P1412

[3] Niemann-Pick C1 disease gene: Homology to mediators of cholesterol homeostasis [J].

Carstea, ED ;

Morris, JA ;

Coleman, KG ;

Loftus, SK ;

Zhang, D ;

Cummings, C ;

Gu, J ;

Rosenfeld, MA ;

Pavan, WJ ;

Krizman, DB ;

Nagle, J ;

Polymeropoulos, MH ;

Sturley, SL ;

Ioannou, YA ;

Higgins, ME ;

Comly, M ;

Cooney, A ;

Brown, A ;

Kaneski, CR ;

BlanchetteMackie, EJ ;

Dwyer, NK ;

Neufeld, EB ;

Chang, TY ;

Liscum, L ;

Strauss, JF ;

Ohno, K ;

Zeigler, M ;

Carmi, R ;

Sokol, J ;

Markie, D ;

ONeill, RR ;

vanDiggelen, OP ;

Elleder, M ;

Patterson, MC ;

Brady, RO ;

Vanier, MT ;

Pentchev, PG ;

Tagle, DA .

SCIENCE, 1997, 277 (5323) :228-231

[4] Role of Niemann-Pick type C1 protein in intracellular trafficking of low density lipoprotein-derived cholesterol [J].

Cruz, JC ;

Sugii, S ;

Yu, CJ ;

Chang, TY .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (06) :4013-4021

[5]

Dodd J., 1991, PRINCIPLES NEURAL SC, P701

[6] NIEMANN-PICK DISEASE TYPE-C - STUDY ON THE NATURE OF THE CEREBRAL STORAGE PROCESS [J].

ELLEDER, M ;

JIRASEK, A ;

SMID, F ;

LEDVINOVA, J ;

BESLEY, GTN .

ACTA NEUROPATHOLOGICA, 1985, 66 (04) :325-336

[7] CLINICAL SPECTRUM OF NIEMANN-PICK DISEASE TYPE-C [J].

FINK, JK ;

FILLINGKATZ, MR ;

SOKOL, J ;

COGAN, DG ;

PIKUS, A ;

SONIES, B ;

SOONG, B ;

PENTCHEV, PG ;

COMLY, ME ;

BRADY, RO ;

BARTON, NW .

NEUROLOGY, 1989, 39 (08) :1040-1049

[8]

Franklin K B J, 2008, MOUSE BRAIN STEREOTA

[9] Embryonic striatal neurons from Niemann-Pick type C mice exhibit defects in cholesterol metabolism and neurotrophin responsiveness [J].

Henderson, LP ;

Lin, L ;

Prasad, A ;

Paul, CA ;

Chang, TY ;

Maue, RA .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (26) :20179-20187

[10]

HIGASHI Y, 1993, ACTA NEUROPATHOL, V85, P175

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