Beclin-1 improves the cognitive function of mice with alzheimer"s disease

We aimed to investigate the improvement effect of Beclin-1 on the cognitive function of mice with Alzheimer"s disease (AD). Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) were isolated from neonatal umbilical cord tissues. The cells stably overexpressing Beclin-1 were constructe...

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Main Authors: Li SHAO, Qing HE, Xin DU, Qing LI, Siyuan YANG, Chen DONG, Pengju MA
Format: Article
Language:English
Published: Kafkas University, Faculty of Veterinary Medicine 2023-12-01
Series:Kafkas Universitesi Veteriner Fakültesi Dergisi
Subjects:
Online Access:https://vetdergikafkas.org/pdf.php?id=3061
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author Li SHAO
Qing HE
Xin DU
Qing LI
Siyuan YANG
Chen DONG
Pengju MA
author_facet Li SHAO
Qing HE
Xin DU
Qing LI
Siyuan YANG
Chen DONG
Pengju MA
author_sort Li SHAO
collection DOAJ
description We aimed to investigate the improvement effect of Beclin-1 on the cognitive function of mice with Alzheimer"s disease (AD). Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) were isolated from neonatal umbilical cord tissues. The cells stably overexpressing Beclin-1 were constructed, and those of passages 5, 10, and 15 were used. Forty-eight AD mice were randomly divided into AD, P5 hUC-MSCs, P15 hUC-MSCs (P15MSCs) and OE Beclin 1-P15 hUC-MSCs (OE Bec-P15MSCs) groups (n=12). Overexpressing Beclin-1 significantly enhanced the proliferation and migration of MSCs of different passages, and reduced G0/G1 arrest. The OE Bec-P15MSCs group had the longest total distance, the shortest time in forced swimming test, and the largest total food consumption in novelty suppressed feeding test. Transplanting hUC-MSCs and overexpressing Beclin-1 significantly reduced Aβ deposition. The expressions of P-tau (Ser396), P-tau (Ser231) and P-tau (Ser235) were significantly inhibited by hUC-MSCs transplantation and Beclin-1 overexpression, especially in the OE Bec- P15MSCs group. Double positive staining of EdU+/DCX+ cells, EdU+/NeuN+ cells and EdU+/Nestin+ cells significantly increased in the OE Bec-P15MSCs group compared to those in other groups (P<0.05). The activation degrees of astrocytes and microglia were lowest and the superoxide dismutase activity was highest in the OE Bec-P15MSCs group (P<0.05). The protein expression of nuclear factor E2-related factor 2 (Nrf2) in NAD(P) H quinone oxidoreductase 1 and superoxide dismutase 1 in brain tissues significantly rose, while that of Keap-1 was down-regulated in the OE Bec-P15MSCs group (P<0.05). Beclin-1 can partly restore the viability of hUC-MSCs by activating the Nrf2 signaling pathway, thereby enhancing the therapeutic effect of transplantation on AD mice.
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spelling doaj.art-f126e7f268084becb45281d64364c2502024-01-13T17:59:33ZengKafkas University, Faculty of Veterinary MedicineKafkas Universitesi Veteriner Fakültesi Dergisi1309-22512023-12-0130151410.9775/kvfd.2023.300573061Beclin-1 improves the cognitive function of mice with alzheimer"s diseaseLi SHAO0Qing HE1Xin DU2Qing LI3Siyuan YANG4Chen DONG5Pengju MA6Department of Neurology, The Municipal Hospital Affiliated to Xuzhou Medical University, Xuzhou First People’s Hospital, Xuzhou 221116, Jiangsu Province, CHINADepartment of Neurology, The Municipal Hospital Affiliated to Xuzhou Medical University, Xuzhou First People’s Hospital, Xuzhou 221116, Jiangsu Province, CHINADepartment of Neurology, The Municipal Hospital Affiliated to Xuzhou Medical University, Xuzhou First People’s Hospital, Xuzhou 221116, Jiangsu Province, CHINADepartment of Neurology, The Municipal Hospital Affiliated to Xuzhou Medical University, Xuzhou First People’s Hospital, Xuzhou 221116, Jiangsu Province, CHINADepartment of Neurology, The Municipal Hospital Affiliated to Xuzhou Medical University, Xuzhou First People’s Hospital, Xuzhou 221116, Jiangsu Province, CHINADepartment of Neurology, The Municipal Hospital Affiliated to Xuzhou Medical University, Xuzhou First People’s Hospital, Xuzhou 221116, Jiangsu Province, CHINALinguistics and Applied Linguistics, School of Liberal Arts, Nanjing Normal University, Nanjing 210000, Jiangsu Province, CHINAWe aimed to investigate the improvement effect of Beclin-1 on the cognitive function of mice with Alzheimer"s disease (AD). Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) were isolated from neonatal umbilical cord tissues. The cells stably overexpressing Beclin-1 were constructed, and those of passages 5, 10, and 15 were used. Forty-eight AD mice were randomly divided into AD, P5 hUC-MSCs, P15 hUC-MSCs (P15MSCs) and OE Beclin 1-P15 hUC-MSCs (OE Bec-P15MSCs) groups (n=12). Overexpressing Beclin-1 significantly enhanced the proliferation and migration of MSCs of different passages, and reduced G0/G1 arrest. The OE Bec-P15MSCs group had the longest total distance, the shortest time in forced swimming test, and the largest total food consumption in novelty suppressed feeding test. Transplanting hUC-MSCs and overexpressing Beclin-1 significantly reduced Aβ deposition. The expressions of P-tau (Ser396), P-tau (Ser231) and P-tau (Ser235) were significantly inhibited by hUC-MSCs transplantation and Beclin-1 overexpression, especially in the OE Bec- P15MSCs group. Double positive staining of EdU+/DCX+ cells, EdU+/NeuN+ cells and EdU+/Nestin+ cells significantly increased in the OE Bec-P15MSCs group compared to those in other groups (P<0.05). The activation degrees of astrocytes and microglia were lowest and the superoxide dismutase activity was highest in the OE Bec-P15MSCs group (P<0.05). The protein expression of nuclear factor E2-related factor 2 (Nrf2) in NAD(P) H quinone oxidoreductase 1 and superoxide dismutase 1 in brain tissues significantly rose, while that of Keap-1 was down-regulated in the OE Bec-P15MSCs group (P<0.05). Beclin-1 can partly restore the viability of hUC-MSCs by activating the Nrf2 signaling pathway, thereby enhancing the therapeutic effect of transplantation on AD mice.https://vetdergikafkas.org/pdf.php?id=3061agingalzheimer"s diseasebeclin-1mesenchymal stem cell
spellingShingle Li SHAO
Qing HE
Xin DU
Qing LI
Siyuan YANG
Chen DONG
Pengju MA
Beclin-1 improves the cognitive function of mice with alzheimer"s disease
Kafkas Universitesi Veteriner Fakültesi Dergisi
aging
alzheimer"s disease
beclin-1
mesenchymal stem cell
title Beclin-1 improves the cognitive function of mice with alzheimer"s disease
title_full Beclin-1 improves the cognitive function of mice with alzheimer"s disease
title_fullStr Beclin-1 improves the cognitive function of mice with alzheimer"s disease
title_full_unstemmed Beclin-1 improves the cognitive function of mice with alzheimer"s disease
title_short Beclin-1 improves the cognitive function of mice with alzheimer"s disease
title_sort beclin 1 improves the cognitive function of mice with alzheimer s disease
topic aging
alzheimer"s disease
beclin-1
mesenchymal stem cell
url https://vetdergikafkas.org/pdf.php?id=3061
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