کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
6262383 1613796 2016 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Research reportSpecific age-related molecular alterations in the cerebellum of Down syndrome mouse models
ترجمه فارسی عنوان
گزارش تحقیق تغییرات مولکولی مرتبط با سن در مخچه مدل موش سندرم داون
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
چکیده انگلیسی


- Altered molecular levels of glial and neuronal proteins in the cerebellum at middle-age.
- Trisomy-specific age-related increase for S100B, in two gene copy.
- Contribution of Pcp4 dosage to GFAP trisomy-specific level with age.
- Increased level of S100B with age in the Ts1Cje is associated to its presence in oligodendrocytes.

Down syndrome, or trisomy 21, has been modeled with various trisomic and transgenic mice to help understand the consequences of an altered gene dosage in brain development and function. Though Down syndrome has been associated with premature aging, little is known about the molecular and cellular alterations that target brain function. To help identify alterations at specific ages, we analyzed the cerebellum of Ts1Cje mice, trisomic for 77 HSA21 orthologs, at three ages-young (4 months), middle-age (12 months), and old (17 months)-compared to age-matched controls. Quantification of neuronal and glial markers (n=11) revealed increases in GFAP, with an age effect, and S100B, with age and genotype effects. The genotype effect on S100B with age was unexpected as Ts1Cje has only two copies of the S100b gene. Interestingly, the different increase in GFAP observed between Ts1Cje (trisomic segment includes Pcp4 gene) and controls was magnified in TgPCP4 mice (1 extra copy of the human PCP4 gene) at the same age. S100B increase was not found in the TgPCP4 confirming a difference of regulation with aging for GFAP and S100B and excluding the calcium signaling regulator, Pcp4, as a potential candidate for increase of S100B in the Ts1Cje. To understand these differences, comparison of GFAP and S100B immunostainings at young and middle-age were performed. Immunohistochemical detection of differences in GFAP and S100B localization with aging implicate S100B+ oligodendrocytes as a new phenotypic target in this specific aging process.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Brain Research - Volume 1646, 1 September 2016, Pages 342-353
نویسندگان
, , , , , ,