سلول های نوروتروفیک باعث افزایش نوروژنز اندوژوس از طریق محور Wnt/b-catenin در مدل موش آلزایمر می شوند.

Neurotrophic factor-secreting cells restored endogenous hippocampal neurogenesis through the Wnt/β-catenin signaling pathway in AD model mice


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نویسندگان: گزل بهلکه , رضا رهبرقاضی , علی عابدالهی , سعید صدیق اعتقاد , محمد کریمی پور

کلمات کلیدی: Alzheimer's disease; Conditioned media; Neurogenesis; Neurotrophic factor-secreting cells; Wnt/β-catenin

نشریه: 32286 , 2022 , 13 , 2022

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نویسنده ثبت کننده مقاله محمد کریمی پور
مرحله جاری مقاله تایید نهایی
دانشکده/مرکز مربوطه دانشکده علوم نوین پزشکی
کد مقاله 79207
عنوان فارسی مقاله سلول های نوروتروفیک باعث افزایش نوروژنز اندوژوس از طریق محور Wnt/b-catenin در مدل موش آلزایمر می شوند.
عنوان لاتین مقاله Neurotrophic factor-secreting cells restored endogenous hippocampal neurogenesis through the Wnt/β-catenin signaling pathway in AD model mice
ناشر 5
آیا مقاله از طرح تحقیقاتی و یا منتورشیپ استخراج شده است؟ بلی
عنوان نشریه (خارج از لیست فوق)
نوع مقاله Original Article
نحوه ایندکس شدن مقاله ایندکس شده سطح یک – ISI - Web of Science
آدرس لینک مقاله/ همایش در شبکه اینترنت

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Background: Impairment in neurogenesis correlates with memory and cognitive dysfunction in AD patients. In the recent decade, therapies with stem cell bases are growing and proved to be efficient. This study is a preliminary attempt to explore the impact of NTF-SCs on hippocampal neurogenesis mediated by the Wnt/β-catenin signaling cascade in AD-like mouse brain parenchyma. Methods: The BALB/c mice were divided into four groups: Control, AD +Vehicle, AD+ TF-SCs-CM and AD+NTF-SCs (n = 10). For AD induction, 100 µM Aβ1-42 was injected into lateral ventricles. The AD-like model was confirmed via passive avoidance test and Thioflavin-S staining 21 days following Aβ injection. Next, NTF-SCs were differentiated from ADMSCs, and both NTF-SCs and supernatant (NTF-SCs-CM) were injected into the hippocampus after AD confirmation. Endogenous neural stem cells (NSCs) proliferation capacity was assessed after 50 mg/kbW BrdU injection for 4 days using immunofluorescence (IF) staining. The percent of BrdU/Nestin and BrdU/NeuN positive NSCs were calculated. Real-time RT-PCR was used to detect genes related to the Wnt/β-catenin signaling cascade. The spatial learning and memory alternation was evaluated using the Morris water maze (MWM). Results: Data showed the reduction in escape latency over 5 days in the AD mice compared to the control group. The administration of NTF-SCs and NTF-SCs-CM increased this value compared to the AD-Vehicle group. Both NTF-SCs and NTF-SCs-CM were the potential to reduce the cumulative distance to the platform in AD mice compared to the AD-Vehicle group. The time spent in target quadrants was ameliorated following NTF-SCs and NTF-SCs-CM transplantation followed by an improved MWM performance. IF imaging revealed the increase in BrdU/Nestin+ and BrdU/NeuN+ in AD mice that received NTF-SCs and NTF-SCs-CM, indicating enhanced neurogenesis. Based on real-time PCR analysis, the expression of PI3K, Akt, MAPK, ERK, Wnt, and β-catenin was upregulated and coincided with the suppression of GSK-3β after injection of NTF-SCs-CM and NTF-SCs. In this study, NTF-SCs had superior effects in AD mice that received NTF-SCs compared to NTF-SCs-CM. Conclusions: The activation of Wnt/β-catenin pathway via NTF-SCs can be touted as a possible therapeutic approach to restore neurogenesis in AD mice.

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نویسنده نفر چندم مقاله
گزل بهلکهاول
رضا رهبرقاضیدوم
علی عابدالهیسوم
سعید صدیق اعتقادچهارم
محمد کریمی پورپنجم

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