کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8841234 | 1614709 | 2017 | 32 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Postnatal Proteasome Inhibition Promotes Amyloid-β Aggregation in Hippocampus and Impairs Spatial Learning in Adult Mice
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کلمات کلیدی
APP-CTFPSDEGTAMVBSMG132MWMBDNF - BDNF یا فاکتور نورونزایی مشتقشده از مغز EDTA - اتیلن دی آمین تترا استیک اسید Ethylenediaminetetraacetic acid - اتیلینیدامین تتراستیک اسیدmultivesicular bodies - بدن مولکولیpostsynaptic density - تراکم Postinapticlong-term potentiation - تقویت درازمدتLTP - تقویت طولانی مدت یا LTP Ubiquitin-proteasome system - سیستم Ubiquitin-proteasomeMorris water maze - ماز آب آب موریسProteasome - پروتئازومSpatial learning - یادگیری فضاییUPS - یو پی اس
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Ubiquitin-proteasome system (UPS) has emerged as major molecular mechanism which modulates synaptic plasticity. However, very little is known about what happens if this system fails during postnatal brain development. In the present study, MG132 was administered intracerebroventricularly in BALB/c mice pups at postnatal day one (P1), a very crucial period for synaptogenesis. Both 20S proteasome and calpain activities were found to be reduced in the mid brain of MG132-administered pups after 24â¯h. Mice (P40) which received MG132 on P1 were subjected to Morris water maze (MWM) training. Analysis showed spatial learning and memory of MG132 mice was significantly impaired when compared to age-matched controls. Hematoxylin and eosin as well as Cresyl Violet staining revealed substantial loss of cellular connections, distorted architecture and increased pyknosis in hippocampal CA1 and CA3 regions of MG132 mice. Immunohistochemical analysis of MG132 mice showed increased accumulation of intracellular amyloid-β in hippocampal cells when compared to control. Moreover, double immunostaining revealed increased expression of amyloid precursor protein C-terminal fragments (APP-CTFβ) without affecting β-secretase expression in MG132 mice. Real-Time PCR analyses showed significant increase in hippocampal expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit glutamate A1 (GluA1), but no change in the brain-derived neurotrophic factor (Bdnf) expression in MG132 mice. Western blot analyses showed decreased levels of pThr286-CaMKIIα:CaMKIIα and pSer133-CREB:CREB ratio but increased pro:mature BDNF ratio in the hippocampus of MG132 mice. Taken together, postnatal proteasome inhibition could lead to accumulation of intracellular amyloid-β protein aggregates, which mediate hippocampus-dependent spatial memory impairments in adult mice.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience - Volume 367, 26 December 2017, Pages 47-59
Journal: Neuroscience - Volume 367, 26 December 2017, Pages 47-59
نویسندگان
Aditya Sunkaria, Aarti Yadav, Supriya Bhardwaj, Rajat Sandhir,