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Maternal Cognitive Impairment Associated with Gestational Diabetes Mellitus—A Review of Potential Contributing Mechanisms

Gestational diabetes mellitus (GDM) carries many risks, where high blood pressure, preeclampsia and future type II diabetes are widely acknowledged, but less focus has been placed on its effect on cognitive function. Although the multifactorial pathogenesis of maternal cognitive impairment is not co...

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Autores principales: John, Cini Mathew, Mohamed Yusof, Nur Intan Saidaah, Abdul Aziz, Siti Hajar, Mohd Fauzi, Fazlin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321050/
https://www.ncbi.nlm.nih.gov/pubmed/30563117
http://dx.doi.org/10.3390/ijms19123894
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author John, Cini Mathew
Mohamed Yusof, Nur Intan Saidaah
Abdul Aziz, Siti Hajar
Mohd Fauzi, Fazlin
author_facet John, Cini Mathew
Mohamed Yusof, Nur Intan Saidaah
Abdul Aziz, Siti Hajar
Mohd Fauzi, Fazlin
author_sort John, Cini Mathew
collection PubMed
description Gestational diabetes mellitus (GDM) carries many risks, where high blood pressure, preeclampsia and future type II diabetes are widely acknowledged, but less focus has been placed on its effect on cognitive function. Although the multifactorial pathogenesis of maternal cognitive impairment is not completely understood, it shares several features with type 2 diabetes mellitus (T2DM). In this review, we discuss some key pathophysiologies of GDM that may lead to cognitive impairment, specifically hyperglycemia, insulin resistance, oxidative stress, and neuroinflammation. We explain how these incidents: (i) impair the insulin-signaling pathway and/or (ii) lead to cognitive impairment through hyperphosphorylation of τ protein, overexpression of amyloid-β and/or activation of microglia. The aforementioned pathologies impair the insulin-signaling pathway primarily through serine phosphorylation of insulin receptor substances (IRS). This then leads to the inactivation of the phosphatidylinositol 3-kinase/Protein kinase B (PI3K/AKT) signaling cascade, which is responsible for maintaining brain homeostasis and normal cognitive functioning. PI3K/AKT is crucial in maintaining normal cognitive function through the inactivation of glycogen synthase kinase 3β (GSκ3β), which hyperphosphorylates τ protein and releases pro-inflammatory cytokines that are neurotoxic. Several biomarkers were also highlighted as potential biomarkers of GDM-related cognitive impairment such as AGEs, serine-phosphorylated IRS-1 and inflammatory markers such as tumor necrosis factor α (TNF-α), high-sensitivity C-reactive protein (hs-CRP), leptin, interleukin 1β (IL-1β), and IL-6. Although GDM is a transient disease, its complications may be long-term, and hence increased mechanistic knowledge of the molecular changes contributing to cognitive impairment may provide important clues for interventional strategies.
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spelling pubmed-63210502019-01-07 Maternal Cognitive Impairment Associated with Gestational Diabetes Mellitus—A Review of Potential Contributing Mechanisms John, Cini Mathew Mohamed Yusof, Nur Intan Saidaah Abdul Aziz, Siti Hajar Mohd Fauzi, Fazlin Int J Mol Sci Review Gestational diabetes mellitus (GDM) carries many risks, where high blood pressure, preeclampsia and future type II diabetes are widely acknowledged, but less focus has been placed on its effect on cognitive function. Although the multifactorial pathogenesis of maternal cognitive impairment is not completely understood, it shares several features with type 2 diabetes mellitus (T2DM). In this review, we discuss some key pathophysiologies of GDM that may lead to cognitive impairment, specifically hyperglycemia, insulin resistance, oxidative stress, and neuroinflammation. We explain how these incidents: (i) impair the insulin-signaling pathway and/or (ii) lead to cognitive impairment through hyperphosphorylation of τ protein, overexpression of amyloid-β and/or activation of microglia. The aforementioned pathologies impair the insulin-signaling pathway primarily through serine phosphorylation of insulin receptor substances (IRS). This then leads to the inactivation of the phosphatidylinositol 3-kinase/Protein kinase B (PI3K/AKT) signaling cascade, which is responsible for maintaining brain homeostasis and normal cognitive functioning. PI3K/AKT is crucial in maintaining normal cognitive function through the inactivation of glycogen synthase kinase 3β (GSκ3β), which hyperphosphorylates τ protein and releases pro-inflammatory cytokines that are neurotoxic. Several biomarkers were also highlighted as potential biomarkers of GDM-related cognitive impairment such as AGEs, serine-phosphorylated IRS-1 and inflammatory markers such as tumor necrosis factor α (TNF-α), high-sensitivity C-reactive protein (hs-CRP), leptin, interleukin 1β (IL-1β), and IL-6. Although GDM is a transient disease, its complications may be long-term, and hence increased mechanistic knowledge of the molecular changes contributing to cognitive impairment may provide important clues for interventional strategies. MDPI 2018-12-05 /pmc/articles/PMC6321050/ /pubmed/30563117 http://dx.doi.org/10.3390/ijms19123894 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
John, Cini Mathew
Mohamed Yusof, Nur Intan Saidaah
Abdul Aziz, Siti Hajar
Mohd Fauzi, Fazlin
Maternal Cognitive Impairment Associated with Gestational Diabetes Mellitus—A Review of Potential Contributing Mechanisms
title Maternal Cognitive Impairment Associated with Gestational Diabetes Mellitus—A Review of Potential Contributing Mechanisms
title_full Maternal Cognitive Impairment Associated with Gestational Diabetes Mellitus—A Review of Potential Contributing Mechanisms
title_fullStr Maternal Cognitive Impairment Associated with Gestational Diabetes Mellitus—A Review of Potential Contributing Mechanisms
title_full_unstemmed Maternal Cognitive Impairment Associated with Gestational Diabetes Mellitus—A Review of Potential Contributing Mechanisms
title_short Maternal Cognitive Impairment Associated with Gestational Diabetes Mellitus—A Review of Potential Contributing Mechanisms
title_sort maternal cognitive impairment associated with gestational diabetes mellitus—a review of potential contributing mechanisms
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321050/
https://www.ncbi.nlm.nih.gov/pubmed/30563117
http://dx.doi.org/10.3390/ijms19123894
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