Evaluation of dihydrotestosterone and dihydroprogesterone levels and gene expression of genes involved in neurosteroidogenesis in the SH-SY5Y Alzheimer disease cell model

IntroductionAlzheimer’s disease (AD) is the most common form of dementia worldwide. This study investigated the effects of lipopolysaccharide on neurosteroidogenesis and its relationship to growth and differentiation using SH-SY5Y cells.MethodsIn this study, we used the MTT assay to assess the impac...

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Main Authors: Saeed Radagdam, Fatemeh Khaki-Khatibi, Reza Rahbarghazi, Behrouz Shademan, Seyed Manouchehr Nourazarian, Masoud Nikanfar, Alireza Nourazarian
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-05-01
Series:Frontiers in Neuroscience
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fnins.2023.1163806/full
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author Saeed Radagdam
Saeed Radagdam
Fatemeh Khaki-Khatibi
Reza Rahbarghazi
Behrouz Shademan
Seyed Manouchehr Nourazarian
Masoud Nikanfar
Alireza Nourazarian
author_facet Saeed Radagdam
Saeed Radagdam
Fatemeh Khaki-Khatibi
Reza Rahbarghazi
Behrouz Shademan
Seyed Manouchehr Nourazarian
Masoud Nikanfar
Alireza Nourazarian
author_sort Saeed Radagdam
collection DOAJ
description IntroductionAlzheimer’s disease (AD) is the most common form of dementia worldwide. This study investigated the effects of lipopolysaccharide on neurosteroidogenesis and its relationship to growth and differentiation using SH-SY5Y cells.MethodsIn this study, we used the MTT assay to assess the impact of LPS on SH-SY5Y cell viability. We also evaluated apoptotic effects using FITC Annexin V staining to detect phosphatidylserine in the cell membrane. To identify gene expression related to human neurogenesis, we utilized the RT2 Profiler TM PCR array human neurogenesis PAHS-404Z.ResultsOur study found that LPS had an IC50 level of 0.25 μg/mL on the SH-SY5Y cell line after 48 h. We observed Aβ deposition in SH-SY5Y cells treated with LPS, and a decrease in DHT and DHP levels in the cells. Our analysis showed that the total rate of apoptosis varied with LPS dilution: 4.6% at 0.1 μg/mL, 10.5% at 10 μg/mL, and 44.1% at 50 μg/mL. We also observed an increase in the expression of several genes involved in human neurogenesis, including ASCL1, BCL2, BDNF, CDK5R1, CDK5RAP2, CREB1, DRD2, HES1, HEYL, NOTCH1, STAT3, and TGFB1, after treatment with LPS at 10 μg/mL and 50 μg/mL. LPS at 50 μg/mL increased the expression of FLNA and NEUROG2, as well as the other genes mentioned.ConclusionOur study showed that LPS treatment altered the expression of human neurogenesis genes and decreased DHT and DHP levels in SH-SY5Y cells. These findings suggest that targeting LPS, DHT, and DHP could be potential therapeutic strategies to treat AD or improve its symptoms.
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spelling doaj.art-7b83638ec7704f4eb8cdfa493a218a5c2023-05-26T13:36:25ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2023-05-011710.3389/fnins.2023.11638061163806Evaluation of dihydrotestosterone and dihydroprogesterone levels and gene expression of genes involved in neurosteroidogenesis in the SH-SY5Y Alzheimer disease cell modelSaeed Radagdam0Saeed Radagdam1Fatemeh Khaki-Khatibi2Reza Rahbarghazi3Behrouz Shademan4Seyed Manouchehr Nourazarian5Masoud Nikanfar6Alireza Nourazarian7Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, IranStem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, IranDepartment of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, IranDepartment of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, IranStem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, IranImam Reza Medical Research and Training Hospital, Tabriz University of Medical Sciences, Tabriz, IranDepartment of Neurology, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, IranDepartment of Basic Medical Sciences, Khoy University of Medical Sciences, Khoy, IranIntroductionAlzheimer’s disease (AD) is the most common form of dementia worldwide. This study investigated the effects of lipopolysaccharide on neurosteroidogenesis and its relationship to growth and differentiation using SH-SY5Y cells.MethodsIn this study, we used the MTT assay to assess the impact of LPS on SH-SY5Y cell viability. We also evaluated apoptotic effects using FITC Annexin V staining to detect phosphatidylserine in the cell membrane. To identify gene expression related to human neurogenesis, we utilized the RT2 Profiler TM PCR array human neurogenesis PAHS-404Z.ResultsOur study found that LPS had an IC50 level of 0.25 μg/mL on the SH-SY5Y cell line after 48 h. We observed Aβ deposition in SH-SY5Y cells treated with LPS, and a decrease in DHT and DHP levels in the cells. Our analysis showed that the total rate of apoptosis varied with LPS dilution: 4.6% at 0.1 μg/mL, 10.5% at 10 μg/mL, and 44.1% at 50 μg/mL. We also observed an increase in the expression of several genes involved in human neurogenesis, including ASCL1, BCL2, BDNF, CDK5R1, CDK5RAP2, CREB1, DRD2, HES1, HEYL, NOTCH1, STAT3, and TGFB1, after treatment with LPS at 10 μg/mL and 50 μg/mL. LPS at 50 μg/mL increased the expression of FLNA and NEUROG2, as well as the other genes mentioned.ConclusionOur study showed that LPS treatment altered the expression of human neurogenesis genes and decreased DHT and DHP levels in SH-SY5Y cells. These findings suggest that targeting LPS, DHT, and DHP could be potential therapeutic strategies to treat AD or improve its symptoms.https://www.frontiersin.org/articles/10.3389/fnins.2023.1163806/fullAlzheimer’s diseaselipopolysaccharidedihydrotestosteronedihydroprogesteronehuman neurogenesis
spellingShingle Saeed Radagdam
Saeed Radagdam
Fatemeh Khaki-Khatibi
Reza Rahbarghazi
Behrouz Shademan
Seyed Manouchehr Nourazarian
Masoud Nikanfar
Alireza Nourazarian
Evaluation of dihydrotestosterone and dihydroprogesterone levels and gene expression of genes involved in neurosteroidogenesis in the SH-SY5Y Alzheimer disease cell model
Frontiers in Neuroscience
Alzheimer’s disease
lipopolysaccharide
dihydrotestosterone
dihydroprogesterone
human neurogenesis
title Evaluation of dihydrotestosterone and dihydroprogesterone levels and gene expression of genes involved in neurosteroidogenesis in the SH-SY5Y Alzheimer disease cell model
title_full Evaluation of dihydrotestosterone and dihydroprogesterone levels and gene expression of genes involved in neurosteroidogenesis in the SH-SY5Y Alzheimer disease cell model
title_fullStr Evaluation of dihydrotestosterone and dihydroprogesterone levels and gene expression of genes involved in neurosteroidogenesis in the SH-SY5Y Alzheimer disease cell model
title_full_unstemmed Evaluation of dihydrotestosterone and dihydroprogesterone levels and gene expression of genes involved in neurosteroidogenesis in the SH-SY5Y Alzheimer disease cell model
title_short Evaluation of dihydrotestosterone and dihydroprogesterone levels and gene expression of genes involved in neurosteroidogenesis in the SH-SY5Y Alzheimer disease cell model
title_sort evaluation of dihydrotestosterone and dihydroprogesterone levels and gene expression of genes involved in neurosteroidogenesis in the sh sy5y alzheimer disease cell model
topic Alzheimer’s disease
lipopolysaccharide
dihydrotestosterone
dihydroprogesterone
human neurogenesis
url https://www.frontiersin.org/articles/10.3389/fnins.2023.1163806/full
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