کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6021765 | 1580649 | 2015 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Phenotypic characterization of a Csf1r haploinsufficient mouse model of adult-onset leukodystrophy with axonal spheroids and pigmented glia (ALSP)
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کلمات کلیدی
PBSPDGFRαOLPIL-34NPCGM-CSFIBA1CSF-1RHDLSLIFPFAgranulocyte-CSFALSPMBPGFAPlateral ventricle - بطن جانبیDysmyelination - دیسمولیناسینNeural progenitor cells - سلولهای پیش گیاه عصبیleukemia inhibitory factor - عامل مهارکننده لوکمیG-CSF - فاکتور محرک کُلونی گرانولوسیتPhosphate buffered saline - فسفات بافر شورpold - لهستانیLeukodystrophy - لکوودیستروفیionized calcium binding adaptor molecule 1 - مولکول آداپتور اتصال دهنده کلسیم یونیزه 1Microglia - میکروگلیاهاfractional anisotropy - ناپیوستگی کسریparaformaldehyde - پارافرمالدهیدGlial fibrillary acidic protein - پروتئین اسیدی فیبریلاسیون گلایالMyelin basic protein - پروتئین پایه میلینOligodendrocyte precursors - پیش سازهای اولیگودندروسیتplatelet-derived growth factor receptor α - گیرنده عامل فاکتور رشد فاکتور αcolony stimulating factor-1 receptor - گیرنده فاکتور 1 تحریک کننده کلنی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
عصب شناسی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Mutations in the colony stimulating factor-1 receptor (CSF1R) that abrogate the expression of the affected allele or lead to the expression of mutant receptor chains devoid of kinase activity have been identified in both familial and sporadic cases of ALSP. To determine the validity of the Csf1r heterozygous mouse as a model of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) we performed behavioral, radiologic, histopathologic, ultrastructural and cytokine expression studies of young and old Csf1r +/â and control Csf1r +/+ mice. Six to 8-month old Csf1r +/â mice exhibit cognitive deficits, and by 9-11 months develop sensorimotor deficits and in male mice, depression and anxiety-like behavior. MRIs of one year-old Csf1r +/â mice reveal lateral ventricle enlargement and thinning of the corpus callosum. Ultrastructural analysis of the corpus callosum uncovers dysmyelinated axons as well as neurodegeneration, evidenced by the presence of axonal spheroids. Histopathological examination of 11-week-old mice reveals increased axonal and myelin staining in the cortex, increase of neuronal cell density in layer V and increase of microglial cell densities throughout the brain, suggesting that early developmental changes contribute to disease. By 10-months of age, the neuronal cell density normalizes, oligodendrocyte precursor cells increase in layers II-III and V and microglial densities remain elevated without an increase in astrocytes. Also, the age-dependent increase in CSF-1R + neurons in cortical layer V is reduced. Moreover, the expression of Csf2, Csf3, Il27 and Il6 family cytokines is increased, consistent with microglia-mediated inflammation. These results demonstrate that the inactivation of one Csf1r allele is sufficient to cause an ALSP-like disease in mice. The Csf1r +/â mouse is a model of ALSP that will allow the critical events for disease development to be determined and permit rapid evaluation of therapeutic approaches. Furthermore, our results suggest that aberrant activation of microglia in Csf1r +/â mice may play a central role in ALSP pathology.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Disease - Volume 74, February 2015, Pages 219-228
Journal: Neurobiology of Disease - Volume 74, February 2015, Pages 219-228
نویسندگان
Violeta Chitu, Solen Gokhan, Maria Gulinello, Craig A. Branch, Madhuvati Patil, Ranu Basu, Corrina Stoddart, Mark F. Mehler, E. Richard Stanley,