کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8837970 | 1612896 | 2018 | 42 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Alpha-Synuclein transgenic mice, h-α-SynL62, display α-Syn aggregation and a dopaminergic phenotype reminiscent of Parkinson's disease
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کلمات کلیدی
VGLUT1substantia nigra pars reticulateDATα-SynDOPACVMAT2Q-RT-PCR3,4-dihydroxyphenylacetic acid - 3،4-دی هیدروکسی فنیل اسیدهای اسیدSNpc - SNPCSNpr - SNPRα-synuclein - α-سینوکلینAlpha-synuclein - آلفا سینوئولینMotor dysfunction - اختلال در عملکرد موتورγ-aminobutyric acid - اسید γ-آمینوبوتیریکDopamine transporter - انتقال دهنده دوپامینParkinson’s disease - بیماری پارکینسونprotein aggregation - تجمع پروتئینsubstantia nigra pars compacta - توده سیاه پارس متراکمtyrosine hydroxylase - تیروزین هیدروکسیلازvesicular glutamate transporter 1 - حمل کننده گلوتامات وزیکولار 1Dopamine - دوپامینvesicular monoamine transporter 2 - مونوآمین حامل 2Dopamine receptor type 2 - نوع دوم گیرنده دوپامینdopamine receptor type 1 - نوع گیرنده دوپامین 1homovanillic acid - هومووانیلیک اسیدQuantitative reverse transcriptase polymerase chain reaction - واکنش زنجیره ای پلی مراز ترانس کریتاز معکوس کمیHVA - چهGABA - گاباglutamate - گلوتاماتD1 receptor - گیرنده D1D2 receptor - گیرنده D2
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب رفتاری
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Alpha-Synuclein transgenic mice, h-α-SynL62, display α-Syn aggregation and a dopaminergic phenotype reminiscent of Parkinson's disease Alpha-Synuclein transgenic mice, h-α-SynL62, display α-Syn aggregation and a dopaminergic phenotype reminiscent of Parkinson's disease](/preview/png/8837970.png)
چکیده انگلیسی
Alpha-Synuclein (α-Syn) accumulation is considered a major risk factor for the development of synucleinopathies such as Parkinson's disease (PD) and dementia with Lewy bodies. We have generated mice overexpressing full-length human α-Syn fused to a membrane-targeting signal sequence under the control of the mouse Thy1-promotor. Three separate lines (L56, L58 and L62) with similar gene expression levels, but considerably heightened protein accumulation in L58 and L62, were established. In L62, there was widespread labelling of α-Syn immunoreactivity in brain including spinal cord, basal forebrain, cortex and striatum. Interestingly, there was no detectable α-Syn expression in dopaminergic neurones of the substantia nigra, but strong human α-Syn reactivity in glutamatergic synapses. The human α-Syn accumulated during aging and formed PK-resistant, thioflavin-binding aggregates. Mice displayed early onset bradykinesia and age progressive motor deficits. Functional alterations within the striatum were confirmed: L62 showed normal basal dopamine levels, but impaired dopamine release (upon amphetamine challenge) in the dorsal striatum measured by in vivo brain dialysis at 9 months of age. This impairment was coincident with a reduced response to amphetamine in the activity test. L62 further displayed greater sensitivity to low doses of the dopamine receptor 1 (D1) agonist SKF81297 but reacted normally to the D2 agonist quinpirole in the open field. Since accumulation of α-Syn aggregates in neurones and synapses and alterations in the dopaminergic tone are characteristics of PD, phenotypes reported for L62 present a good opportunity to further our understanding of motor dysfunction in PD and Lewy body dementia.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Behavioural Brain Research - Volume 339, 26 February 2018, Pages 153-168
Journal: Behavioural Brain Research - Volume 339, 26 February 2018, Pages 153-168
نویسندگان
Silke Frahm, Valeria Melis, David Horsley, Janet E. Rickard, Gernot Riedel, Paula Fadda, Maria Scherma, Charles R. Harrington, Claude M. Wischik, Franz Theuring, Karima Schwab,