کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
4932006 | 1433303 | 2017 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Alterations of ubiquitin related proteins in the pathology and development of schizophrenia: Evidence from human and animal studies
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کلمات کلیدی
PFCUCHL1α-amino-3-hydroxy-5-methyl-4-isoxazolepropionateDLPFCPCPAMPANMDAN-methyl-d-aspartatePSD-95Mdm2 - MDM2Schizophrenia - اسکیزوفرنی یا شیزوفرنیpostnatal days - روزهای پس از تولدRIN - رینUbiquitin proteasome system - سیستم پروتئازوم UbiquitinPMI - شرکتهای کوچک و متوسطPost-mortem interval - فاصله پس از مرگPhencyclidine - فن سیکلیدین، گرد فرشتهprefrontal cortex - قشر prefrontaldorsolateral prefrontal cortex - قشر پیشانی غدد درون رحمیE3 ligases - لیگاز E3mouse double minute 2 homolog - موش دو دقیقه 2 همولوگUPS - یو پی اسRNA integrity - یکپارچگی RNA
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
روانپزشکی بیولوژیکی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Gene expression analyses in post-mortem schizophrenia brains suggest that a number of ubiquitin proteasome system (UPS) genes are associated with schizophrenia; however the status of UPS proteins in the schizophrenia brain is largely unknown. Ubiquitin related proteins are inherently involved in memory, neuronal survival and morphology, which are processes implicated in neurodevelopmental disorders such as schizophrenia. We examined levels of five UPS proteins (Protein Inhibitor of Activated STAT2 [PIAS2], F-Box and Leucine rich repeat protein 21 [FBXL21], Mouse Double Minute 2 homolog [MDM2], Ubiquitin Carboxyl-Terminal Hydrolase-L1 [UCHL1] and Ubiquitin Conjugating Enzyme E2D1 [UBE2D1]) involved in these neuronal processes, within the dorsolateral prefrontal cortex of post-mortem schizophrenia subjects and matched controls (n = 30/group), in addition to across neurodevelopmental time-points (juvenile, adolescent and adult stages of life), utilizing a well-established neurodevelopmental phencyclidine (PCP) animal model of schizophrenia. We observed significant reductions in PIAS2, FBXL21 and MDM2 in schizophrenia subjects compared to controls (p-values ranging from 0.002 to 0.004). In our developmental PCP model, MDM2 protein was significantly reduced in adult PCP-treated rats compared to controls (p = 0.034). Additionally, FBXL21 (p = 0.022) and UCHL1 (p = 0.022) were significantly decreased, whilst UBE2D1 was increased (p = 0.022), in juvenile phencyclidine-treated rats compared to controls. This is the first study reporting alterations of UPS proteins in post-mortem human schizophrenia subjects and in a neurodevelopmental model of schizophrenia. The findings from this study provide strong support for a role of these UPS proteins in the pathology and development of schizophrenia.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Psychiatric Research - Volume 90, July 2017, Pages 31-39
Journal: Journal of Psychiatric Research - Volume 90, July 2017, Pages 31-39
نویسندگان
Jessica L. Andrews, Frederic J. Goodfellow, Natalie Matosin, Mollie K. Snelling, Kelly A. Newell, Xu-Feng Huang, Francesca Fernandez-Enright,