کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9192053 | 1186612 | 2005 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Lentiviral gene delivery of GDNF into the striatum of R6/2 Huntington mice fails to attenuate behavioral and neuropathological changes
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کلمات کلیدی
GFPS.E.M.GDNFCNTFN-methyl-d-aspartate6-HydroxydopaminePFA3-NPNMDADABDARPP-326-OHDA3′-diaminobenzidineNGF3-nitropropionic acid - 3-اسید نیتروپروپیونیکBDNF - BDNF یا فاکتور نورونزایی مشتقشده از مغز Striatum - استریاتومγ-aminobutyric acid - اسید γ-آمینوبوتیریکphosphate buffer - بافر فسفاتBrdU - بروموداکسی اوریدینbromodeoxyuridine - برومودسوویریدینHuntington’s disease - بیماری هانتینگتونHuntington disease - بیماری هانتینگتونanalysis of variance - تحلیل واریانسANOVA - تحلیل واریانس Analysis of varianceEnzyme-linked immunosorbent assay - تست الیزاELISA - تست الیزاstandard error of mean - خطای استاندارد میانگینBehavior - رفتارnerve growth factor - فاکتور رشد عصبGlial cell line-derived neurotrophic factor - فاکتور نوروتروفی مشتق از سلول گلیاییBrain-derived neurotrophic factor - فاکتور نوروتروفی مشتق شده از مغزciliary neurotrophic factor - فاکتور نوروتروفیک ciliaryparaformaldehyde - پارافرمالدهیدgreen fluorescent protein - پروتئین فلورسنت سبزGene therapy - ژن درمانیGABA - گابا
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
عصب شناسی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Transgenic R6/2 mice, which express exon 1 of the human mutant Huntington disease gene, develop behavioral and neuropathological changes that bear some resemblance to the human disease. Several studies have shown that elevated glial cell line-derived neurotrophic factor (GDNF) levels can exert neuroprotective effects in animal models of Huntington disease that are based on intrastriatal injections of excitotoxins. Therefore, the aim of the present study was to examine whether intrastriatal delivery of the GDNF gene by lentivirus (LV-GDNF) could provide structural and functional protection in R6/2 transgenic mice. Four- to 5-week-old mice were left untreated or alternatively received intrastriatal injections of either LV-GDNF or the same viral vector encoding green fluorescent protein (GFP) (LV-GFP) as a control. During the 4-week follow-up period, there was the expected deterioration in performance of the R6/2 mice in paw clasping, rotarod, and open field tests, and the LV-GDNF treated mice showed no improvement over controls. ELISA showed that the LV-GDNF-injected animals had a significant increase in GDNF level in the striatum, and immunohistochemical analysis revealed that GDNF was also overexpressed in brain regions receiving striatal projections. However, GDNF overexpression had no effect on the neuropathological changes examined. Thus, there were no significant differences in the number of EM-48-positive intraneuronal huntingtin inclusions, number of BrdU-positive cells and size of striatal neuronal cross-sectional area. These results suggest that intrastriatal lentiviral vector transfer of GDNF, performed at 5 weeks of age, does not ameliorate neurological and behavioral impairments in the R6/2 transgenic mice model of HD. Further studies are, however, needed to investigate if GDNF given at earlier time points is beneficial.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Neurology - Volume 193, Issue 1, May 2005, Pages 65-74
Journal: Experimental Neurology - Volume 193, Issue 1, May 2005, Pages 65-74
نویسندگان
Natalija Popovic, Matthew Maingay, Deniz Kirik, Patrik Brundin,