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Integrated proteomics and metabolomics analysis of D-pinitol function during hippocampal damage in streptozocin-induced aging-accelerated mice

PURPOSE: Diabetes can cause hippocampal damage and lead to cognitive impairment. Diabetic cognitive impairment (DCI) is a chronic complication of diabetes associated with a high disability rate; however, its pathogenesis and therapeutic targets are unclear. We aimed to explore the mechanism of hippo...

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Autores principales: Li, Xiaoxia, Gao, Yuan, Li, Baoying, Zhao, Wenqian, Cai, Qian, Yin, Wenbin, Zeng, Shudong, Li, Xiaoli, Gao, Haiqing, Cheng, Mei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10664147/
https://www.ncbi.nlm.nih.gov/pubmed/38025258
http://dx.doi.org/10.3389/fnmol.2023.1251513
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author Li, Xiaoxia
Gao, Yuan
Li, Baoying
Zhao, Wenqian
Cai, Qian
Yin, Wenbin
Zeng, Shudong
Li, Xiaoli
Gao, Haiqing
Cheng, Mei
author_facet Li, Xiaoxia
Gao, Yuan
Li, Baoying
Zhao, Wenqian
Cai, Qian
Yin, Wenbin
Zeng, Shudong
Li, Xiaoli
Gao, Haiqing
Cheng, Mei
author_sort Li, Xiaoxia
collection PubMed
description PURPOSE: Diabetes can cause hippocampal damage and lead to cognitive impairment. Diabetic cognitive impairment (DCI) is a chronic complication of diabetes associated with a high disability rate; however, its pathogenesis and therapeutic targets are unclear. We aimed to explore the mechanism of hippocampal damage during diabetes and evaluate the potential role of D-pinitol (DP) in protecting hippocampal tissue and improving cognitive dysfunction. METHODS: DP (150 mg/kg/day) was administered intragastrically to streptozocin-induced aging-accelerated mice for 8 weeks. Hippocampal tissues were examined using tandem mass tag (TMT)-based proteomics and liquid chromatography-mass spectrometry (LC–MS)/MS-based non-targeted metabolomic analysis. Differentially expressed proteins (DEPs) and differentially regulated metabolites (DRMs) were screened for further analysis, and some DEPs were verified using western blotting. RESULTS: Our results showed that 329 proteins had significantly altered hippocampal expression in untreated diabetic mice (DM), which was restored to normal after DP treatment in 72 cases. In total, 207 DRMs were identified in the DM group, and the expression of 32 DRMs was restored to normal post-DP treatment. These proteins and metabolites are involved in metabolic pathways (purine metabolism, arginine and proline metabolism, and histidine metabolism), actin cytoskeleton regulation, oxidative phosphorylation, and Rap1-mediated signaling. CONCLUSIONS: Our study may help to better understand the mechanism of diabetic hippocampal damage and cognitive impairment and suggest a potential therapeutic target.
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spelling pubmed-106641472023-01-01 Integrated proteomics and metabolomics analysis of D-pinitol function during hippocampal damage in streptozocin-induced aging-accelerated mice Li, Xiaoxia Gao, Yuan Li, Baoying Zhao, Wenqian Cai, Qian Yin, Wenbin Zeng, Shudong Li, Xiaoli Gao, Haiqing Cheng, Mei Front Mol Neurosci Molecular Neuroscience PURPOSE: Diabetes can cause hippocampal damage and lead to cognitive impairment. Diabetic cognitive impairment (DCI) is a chronic complication of diabetes associated with a high disability rate; however, its pathogenesis and therapeutic targets are unclear. We aimed to explore the mechanism of hippocampal damage during diabetes and evaluate the potential role of D-pinitol (DP) in protecting hippocampal tissue and improving cognitive dysfunction. METHODS: DP (150 mg/kg/day) was administered intragastrically to streptozocin-induced aging-accelerated mice for 8 weeks. Hippocampal tissues were examined using tandem mass tag (TMT)-based proteomics and liquid chromatography-mass spectrometry (LC–MS)/MS-based non-targeted metabolomic analysis. Differentially expressed proteins (DEPs) and differentially regulated metabolites (DRMs) were screened for further analysis, and some DEPs were verified using western blotting. RESULTS: Our results showed that 329 proteins had significantly altered hippocampal expression in untreated diabetic mice (DM), which was restored to normal after DP treatment in 72 cases. In total, 207 DRMs were identified in the DM group, and the expression of 32 DRMs was restored to normal post-DP treatment. These proteins and metabolites are involved in metabolic pathways (purine metabolism, arginine and proline metabolism, and histidine metabolism), actin cytoskeleton regulation, oxidative phosphorylation, and Rap1-mediated signaling. CONCLUSIONS: Our study may help to better understand the mechanism of diabetic hippocampal damage and cognitive impairment and suggest a potential therapeutic target. Frontiers Media S.A. 2023-10-30 /pmc/articles/PMC10664147/ /pubmed/38025258 http://dx.doi.org/10.3389/fnmol.2023.1251513 Text en Copyright © 2023 Li, Gao, Li, Zhao, Cai, Yin, Zeng, Li, Gao and Cheng. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Neuroscience
Li, Xiaoxia
Gao, Yuan
Li, Baoying
Zhao, Wenqian
Cai, Qian
Yin, Wenbin
Zeng, Shudong
Li, Xiaoli
Gao, Haiqing
Cheng, Mei
Integrated proteomics and metabolomics analysis of D-pinitol function during hippocampal damage in streptozocin-induced aging-accelerated mice
title Integrated proteomics and metabolomics analysis of D-pinitol function during hippocampal damage in streptozocin-induced aging-accelerated mice
title_full Integrated proteomics and metabolomics analysis of D-pinitol function during hippocampal damage in streptozocin-induced aging-accelerated mice
title_fullStr Integrated proteomics and metabolomics analysis of D-pinitol function during hippocampal damage in streptozocin-induced aging-accelerated mice
title_full_unstemmed Integrated proteomics and metabolomics analysis of D-pinitol function during hippocampal damage in streptozocin-induced aging-accelerated mice
title_short Integrated proteomics and metabolomics analysis of D-pinitol function during hippocampal damage in streptozocin-induced aging-accelerated mice
title_sort integrated proteomics and metabolomics analysis of d-pinitol function during hippocampal damage in streptozocin-induced aging-accelerated mice
topic Molecular Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10664147/
https://www.ncbi.nlm.nih.gov/pubmed/38025258
http://dx.doi.org/10.3389/fnmol.2023.1251513
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