کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6808384 | 1433592 | 2012 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
The noradrenaline precursor L-DOPS reduces pathology in a mouse model of Alzheimer's disease
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کلمات کلیدی
GFAPDroxidopathioflavin-Sinflammation - التهاب( توروم) tyrosine hydroxylase - تیروزین هیدروکسیلازglial cells - سلول های گلیالlocus coeruleus - لوکوس سیرولئوسMorris water maze - ماز آب آب موریسnoradrenaline - نورآدرنالین Neurotrophin - نوروتروفینNeprilysin - نپریلینLearning and memory - یادگیری و حافظه
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
سالمندی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Damage to noradrenergic neurons in the locus coeruleus (LC) is a hallmark of Alzheimer's disease (AD) and may contribute to disease progression. In 5xFAD transgenic mice, which accumulate amyloid burden at early ages, the LC undergoes stress as evidenced by increased astrocyte activation, neuronal hypertrophy, reduced levels of LC-enriched messenger RNAs (mRNAs), and increased inflammatory gene expression. Central nervous system (CNS) noradrenaline (NA) levels in 5-month-old male 5xFAD mice were increased using the NA precursor L-threo-3,4-dihydroxyphenylserine (L-DOPS). After 1 month, L-DOPS treatment improved learning in the Morris water maze test compared with vehicle-treated mice. L-DOPS increased CNS NA levels, and average latency times in the water maze test were inversely correlated to NA levels. L-DOPS reduced astrocyte activation and Thioflavin-S staining; increased mRNA levels of neprilysin and insulin degrading enzyme, and of several neurotrophins; and increased brain-derived neurotrophic factor protein levels. These data demonstrate the presence of LC stress in a robust mouse model of AD, and suggest that raising CNS NA levels could provide benefit in AD.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Aging - Volume 33, Issue 8, August 2012, Pages 1651-1663
Journal: Neurobiology of Aging - Volume 33, Issue 8, August 2012, Pages 1651-1663
نویسندگان
Sergey Kalinin, Paul E. Polak, Shao Xia Lin, Amul J. Sakharkar, Subhash C. Pandey, Douglas L. Feinstein,