Attenuated plasticity in neurons and astrocytes in the mouse model of Sanfilippo syndrome type B

被引:65
作者
Li, HH
Zhao, HZ
Neufeld, EF
Cai, Y
Gómez-Pinilla, F
机构
[1] Univ Calif Los Angeles, Sch Med, Dept Surg, Div Neurosurg, Los Angeles, CA 90095 USA
[2] Univ Calif Los Angeles, Dept Biol Chem, Los Angeles, CA 90095 USA
[3] Univ Calif Los Angeles, Div Neurosurg, Brain Injury Res Ctr, Los Angeles, CA 90095 USA
[4] Univ Calif Los Angeles, Brain Res Inst, Los Angeles, CA 90095 USA
[5] Univ Calif Los Angeles, Dept Physiol Sci, Los Angeles, CA 90095 USA
关键词
MPS IIIB; FGF; astrocytes; injury; neurogenesis;
D O I
10.1002/jnr.10278
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Sanfilippo syndrome type B (MPS III B) is a neurodegenerative disorder characterized by profound mental retardation and early death. It is caused by deficiency of a lysosomal enzyme involved in heparan sulfate (HS) degradation. Because HS accumulation can be a major feature of this disease, we have examined crucial molecular systems associated with HS function. Using a knockout mouse with disruption of the gene responsible for HS degradation, we evaluated the effects of possible HS accumulation on neuroplasticity that are within the spectrum of action of fibroblast growth factors (FGFs) and their receptor (FGFR). We found that levels of mRNA for the FGFR-1 were attenuated in the mutant mice by the age of 6 months, whereas the mRNAs for FGF-1 and FGF-2 were reduced or unchanged in the brain regions tested. Neurogenesis, in which FGF-2 is involved, was inhibited in the MPS III B mouse brain at both young and adult ages. We also examined the expression of the glial fibrillary acidic protein (GFAP) gene and GFAP-positive cell density in both normal and injured conditions to study the functional response of astrocytes to insult. We found that, although the mutation alone caused drastic induction of reactive astrocytes, acute injury to the mutant brains failed to induce additional reactive astrocytes. Our results showed important alterations in the expression of several genes involved in the maintenance of neuroplasticity in the MPS III B. This in turn may result in reduction of neuronal health and brain function. (C) 2002 Wiley-Liss, Inc.
引用
收藏
页码:30 / 38
页数:9
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