Neurocognitive impairmentin gestational diabetes mellitus: oxidative stress and inflammation as possible mechanism / Nur Intan Saidaah Mohamed Yusof

The correlation between gestational diabetes mellitus (GDM) and cognition is modest. Some individuals remain cognitively intact during the gestational period despite the presence of GDM, whereas others show cognitive impairment and dementia in the same milieu. The aim of the present study was to exa...

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Main Author: Mohamed Yusof, Nur Intan Saidaah
Format: Thesis
Language:English
Published: 2017
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Online Access:https://ir.uitm.edu.my/id/eprint/39285/1/39285.pdf
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spelling my-uitm-ir.392852021-08-30T03:32:37Z Neurocognitive impairmentin gestational diabetes mellitus: oxidative stress and inflammation as possible mechanism / Nur Intan Saidaah Mohamed Yusof 2017-10 Mohamed Yusof, Nur Intan Saidaah Neuroscience. Biological psychiatry. Neuropsychiatry The correlation between gestational diabetes mellitus (GDM) and cognition is modest. Some individuals remain cognitively intact during the gestational period despite the presence of GDM, whereas others show cognitive impairment and dementia in the same milieu. The aim of the present study was to examine the cognitive functions and evaluate the oxidative/inflammatory parameters in early and late stages of gestation in a GDM rat model. GDM has been associated with cognitive impairment as insulin receptors in the brain are located in the hippocampus, which is responsible for memory. Impaired insulin signaling in the brain may induce oxidative stress and inflammation, causing nerve damages and consequently cognitive impairment. In this study, we looked at the oxidative and inflammatory status in the brain of GDM rats on day 14 (D14) and 21 (D21), in addition to brain histology and cognitive function through Morris Water Maze (MWM) test. Gene expression of oxidative stress (SOD, CAT, GPX, p53, Hao-1) and inflammatory markers (IL-6, NF-Kb, IFN-y, TNF-a, PPAR-y, Vegf) were evaluated using quantitative RT-PCR analysis. The result showed that GDM group had a lower expression of antioxidant enzymes (SOD, CAT, GPX) on D14 and D21, and higher expression of Hao-1 and p53 than control. These indicate oxidative stress in brain of GDM rats. High expression of pro-inflammatory genes (IL-6, NF-Kb, IFN-y, TNF-a) and low expression of anti-inflammatory genes (PPAR-y, Vegf) were observed in the GDM group. Furthermore, disruption of normal layer organization, darkened and shrunken nuclei were observed in the hippocampus of GDM group, indicating apoptosis. GDM rats also showed impaired learning and memory function in the MWM test, where GDM rats clocked a longer escape latency time and shorter time spent in target quadrant than control. These findings provide evidence on the impairment of cognitive functions in GDM, which may be due to oxidative stress and inflammation in the brain. 2017-10 Thesis https://ir.uitm.edu.my/id/eprint/39285/ https://ir.uitm.edu.my/id/eprint/39285/1/39285.pdf text en public masters Universiti Teknologi MARA Faculty of Pharmacy John, Cini Mathew (Dr. )
institution Universiti Teknologi MARA
collection UiTM Institutional Repository
language English
advisor John, Cini Mathew (Dr. )
topic Neuroscience
Biological psychiatry
Neuropsychiatry
spellingShingle Neuroscience
Biological psychiatry
Neuropsychiatry
Mohamed Yusof, Nur Intan Saidaah
Neurocognitive impairmentin gestational diabetes mellitus: oxidative stress and inflammation as possible mechanism / Nur Intan Saidaah Mohamed Yusof
description The correlation between gestational diabetes mellitus (GDM) and cognition is modest. Some individuals remain cognitively intact during the gestational period despite the presence of GDM, whereas others show cognitive impairment and dementia in the same milieu. The aim of the present study was to examine the cognitive functions and evaluate the oxidative/inflammatory parameters in early and late stages of gestation in a GDM rat model. GDM has been associated with cognitive impairment as insulin receptors in the brain are located in the hippocampus, which is responsible for memory. Impaired insulin signaling in the brain may induce oxidative stress and inflammation, causing nerve damages and consequently cognitive impairment. In this study, we looked at the oxidative and inflammatory status in the brain of GDM rats on day 14 (D14) and 21 (D21), in addition to brain histology and cognitive function through Morris Water Maze (MWM) test. Gene expression of oxidative stress (SOD, CAT, GPX, p53, Hao-1) and inflammatory markers (IL-6, NF-Kb, IFN-y, TNF-a, PPAR-y, Vegf) were evaluated using quantitative RT-PCR analysis. The result showed that GDM group had a lower expression of antioxidant enzymes (SOD, CAT, GPX) on D14 and D21, and higher expression of Hao-1 and p53 than control. These indicate oxidative stress in brain of GDM rats. High expression of pro-inflammatory genes (IL-6, NF-Kb, IFN-y, TNF-a) and low expression of anti-inflammatory genes (PPAR-y, Vegf) were observed in the GDM group. Furthermore, disruption of normal layer organization, darkened and shrunken nuclei were observed in the hippocampus of GDM group, indicating apoptosis. GDM rats also showed impaired learning and memory function in the MWM test, where GDM rats clocked a longer escape latency time and shorter time spent in target quadrant than control. These findings provide evidence on the impairment of cognitive functions in GDM, which may be due to oxidative stress and inflammation in the brain.
format Thesis
qualification_level Master's degree
author Mohamed Yusof, Nur Intan Saidaah
author_facet Mohamed Yusof, Nur Intan Saidaah
author_sort Mohamed Yusof, Nur Intan Saidaah
title Neurocognitive impairmentin gestational diabetes mellitus: oxidative stress and inflammation as possible mechanism / Nur Intan Saidaah Mohamed Yusof
title_short Neurocognitive impairmentin gestational diabetes mellitus: oxidative stress and inflammation as possible mechanism / Nur Intan Saidaah Mohamed Yusof
title_full Neurocognitive impairmentin gestational diabetes mellitus: oxidative stress and inflammation as possible mechanism / Nur Intan Saidaah Mohamed Yusof
title_fullStr Neurocognitive impairmentin gestational diabetes mellitus: oxidative stress and inflammation as possible mechanism / Nur Intan Saidaah Mohamed Yusof
title_full_unstemmed Neurocognitive impairmentin gestational diabetes mellitus: oxidative stress and inflammation as possible mechanism / Nur Intan Saidaah Mohamed Yusof
title_sort neurocognitive impairmentin gestational diabetes mellitus: oxidative stress and inflammation as possible mechanism / nur intan saidaah mohamed yusof
granting_institution Universiti Teknologi MARA
granting_department Faculty of Pharmacy
publishDate 2017
url https://ir.uitm.edu.my/id/eprint/39285/1/39285.pdf
_version_ 1783734501482954752