Spatial and Temporal Profiles of Growth Factor Expression during CNS Demyelination Reveal the Dynamics of Repair Priming

被引:85
作者
Gudi, Viktoria [1 ,2 ]
Skuljec, Jelena [1 ,2 ]
Yildiz, Oezlem [1 ]
Frichert, Konstantin [1 ]
Skripuletz, Thomas [1 ]
Moharregh-Khiabani, Darius [1 ]
Voss, Elke [1 ]
Wissel, Kirsten [3 ]
Wolter, Sabine [4 ]
Stangel, Martin [1 ,2 ]
机构
[1] Hannover Med Sch, Dept Neurol, D-3000 Hannover, Germany
[2] Ctr Syst Neurosci, Hannover, Germany
[3] Hannover Med Sch, Dept Otolaryngol, D-3000 Hannover, Germany
[4] Hannover Med Sch, Dept Pharmacol, D-3000 Hannover, Germany
来源
PLOS ONE | 2011年 / 6卷 / 07期
关键词
CILIARY NEUROTROPHIC FACTOR; LEUKEMIA INHIBITORY FACTOR; CENTRAL-NERVOUS-SYSTEM; OLIGODENDROCYTE PRECURSOR CELLS; MULTIPLE-SCLEROSIS LESIONS; SPINAL-CORD DEMYELINATION; BRAIN AGGREGATE CULTURES; IN-VIVO; FACTOR GDNF; IGF-I;
D O I
10.1371/journal.pone.0022623
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Demyelination is the cause of disability in various neurological disorders. It is therefore crucial to understand the molecular regulation of oligodendrocytes, the myelin forming cells in the CNS. Growth factors are known to be essential for the development and maintenance of oligodendrocytes and are involved in the regulation of glial responses in various pathological conditions. We employed the well established murine cuprizone model of toxic demyelination to analyze the expression of 13 growth factors in the CNS during de- and remyelination. The temporal mRNA expression profile during demyelination and the subsequent remyelination were analyzed separately in the corpus callosum and cerebral cortex using laser microdissection and real-time PCR techniques. During demyelination a similar pattern of growth factor mRNA expression was observed in both areas with a strong up-regulation of NRG1 and GDNF and a slight increase of CNTF in the first week of cuprizone treatment. HGF, FGF-2, LIF, IGF-1, and TGF-beta 1 were up-regulated mainly during peak demyelination. In contrast, during remyelination there were regional differences in growth factor mRNA expression levels. GDNF, CNTF, HGF, FGF-2, and BDNF were elevated in the corpus callosum but not in the cortex, suggesting tissue differences in the molecular regulation of remyelination in the white and grey matter. To clarify the cellular source we isolated microglia from the cuprizone lesions. GDNF, IGF-1, and FGF mRNA were detected in the microglial fraction with a temporal pattern corresponding to that from whole tissue PCR. In addition, immunohistochemical analysis revealed IGF-1 protein expression also in the reactive astrocytes. CNTF was located in astrocytes. This study identified seven different temporal expression patterns for growth factors in white and grey matter and demonstrated the importance of early tissue priming and exact orchestration of different steps during callosal and cortical de- and remyelination.
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页数:13
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