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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| Format: | Article |
| Language: | English |
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MDPI AG
2018-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/19/12/3894 |
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| author | Cini Mathew John Nur Intan Saidaah Mohamed Yusof Siti Hajar Abdul Aziz Fazlin Mohd Fauzi |
| author_facet | Cini Mathew John Nur Intan Saidaah Mohamed Yusof Siti Hajar Abdul Aziz Fazlin Mohd Fauzi |
| author_sort | Cini Mathew John |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-04-13T00:36:39Z |
| format | Article |
| id | doaj.art-70efcf4958cf46bdba8d72c579d75db6 |
| institution | Directory Open Access Journal |
| issn | 1422-0067 |
| language | English |
| last_indexed | 2024-04-13T00:36:39Z |
| publishDate | 2018-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-70efcf4958cf46bdba8d72c579d75db62022-12-22T03:10:18ZengMDPI AGInternational Journal of Molecular Sciences1422-00672018-12-011912389410.3390/ijms19123894ijms19123894Maternal Cognitive Impairment Associated with Gestational Diabetes Mellitus—A Review of Potential Contributing MechanismsCini Mathew John0Nur Intan Saidaah Mohamed Yusof1Siti Hajar Abdul Aziz2Fazlin Mohd Fauzi3Department of Pharmacology and Chemistry, Faculty of Pharmacy, Universiti Teknologi MARA, Bandar Puncak Alam 42300, Selangor Darul Ehsan, MalaysiaDepartment of Pharmacology and Chemistry, Faculty of Pharmacy, Universiti Teknologi MARA, Bandar Puncak Alam 42300, Selangor Darul Ehsan, MalaysiaDepartment of Pharmacology and Chemistry, Faculty of Pharmacy, Universiti Teknologi MARA, Bandar Puncak Alam 42300, Selangor Darul Ehsan, MalaysiaDepartment of Pharmacology and Chemistry, Faculty of Pharmacy, Universiti Teknologi MARA, Bandar Puncak Alam 42300, Selangor Darul Ehsan, MalaysiaGestational 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.https://www.mdpi.com/1422-0067/19/12/3894gestational diabetes mellituscognitive impairmentneuroinflammationinsulin resistanceoxidative stress |
| spellingShingle | Cini Mathew John Nur Intan Saidaah Mohamed Yusof Siti Hajar Abdul Aziz Fazlin Mohd Fauzi Maternal Cognitive Impairment Associated with Gestational Diabetes Mellitus—A Review of Potential Contributing Mechanisms International Journal of Molecular Sciences gestational diabetes mellitus cognitive impairment neuroinflammation insulin resistance oxidative stress |
| 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 | gestational diabetes mellitus cognitive impairment neuroinflammation insulin resistance oxidative stress |
| url | https://www.mdpi.com/1422-0067/19/12/3894 |
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