Cargando…

Gestational Diabetes Triggers Oxidative Stress in Hippocampus and Cerebral Cortex and Cognitive Behavior Modifications in Rat Offspring: Age- and Sex-Dependent Effects

Gestational diabetes (GD) has been linked with an increased risk of developing metabolic disorders and behavioral abnormalities in the offspring. Oxidative stress is strongly associated with neurodegeneration and cognitive disruption. In the offspring brains in a GD experimental rat model, increased...

Descripción completa

Detalles Bibliográficos
Autores principales: Huerta-Cervantes, Maribel, Peña-Montes, Donovan J., Montoya-Pérez, Rocío, Trujillo, Xóchitl, Huerta, Miguel, López-Vázquez, Miguel Ángel, Olvera-Cortés, María Esther, Saavedra-Molina, Alfredo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7071266/
https://www.ncbi.nlm.nih.gov/pubmed/32023917
http://dx.doi.org/10.3390/nu12020376
_version_ 1783506162300223488
author Huerta-Cervantes, Maribel
Peña-Montes, Donovan J.
Montoya-Pérez, Rocío
Trujillo, Xóchitl
Huerta, Miguel
López-Vázquez, Miguel Ángel
Olvera-Cortés, María Esther
Saavedra-Molina, Alfredo
author_facet Huerta-Cervantes, Maribel
Peña-Montes, Donovan J.
Montoya-Pérez, Rocío
Trujillo, Xóchitl
Huerta, Miguel
López-Vázquez, Miguel Ángel
Olvera-Cortés, María Esther
Saavedra-Molina, Alfredo
author_sort Huerta-Cervantes, Maribel
collection PubMed
description Gestational diabetes (GD) has been linked with an increased risk of developing metabolic disorders and behavioral abnormalities in the offspring. Oxidative stress is strongly associated with neurodegeneration and cognitive disruption. In the offspring brains in a GD experimental rat model, increased oxidative stress in the prenatal and postnatal stages was reported. However, long-term alterations to offspring behavior and oxidative stress, caused by changes in the cerebral cortex and hippocampus, remain unclear. In this study, we evaluated the effect of GD on young and adult male and female rat offspring in metabolic parameters, cognitive behavior, and oxidative stress. GD was induced using streptozotocin in dams. Next, the offspring were evaluated at two and six months of age. Anxiety-like behavior was evaluated using the elevated plus maze and open field maze; spatial learning and short-term memory were evaluated using the Morris water maze and radial maze, respectively. We determined oxidative stress biomarkers (reactive oxygen species (ROS), lipid peroxidation and glutathione status) and antioxidant enzymes (superoxide dismutase and catalase) in the brain of offspring. We observed that male GD offspring showed a reduced level of anxiety at both ages as they spent less time in the closed arms of the elevated plus maze at adult age ((P = 0.019, d = 1.083 ( size effect)) and spent more time in the open area of an open field (P = 0.0412, d = 0.743) when young and adult age (P = 0.018, d = 0.65). Adult female GD offspring showed a reduced level of anxiety (P = 0.036; d = 0.966), and young female GD offspring showed a deficiency in spatial learning (P = 0.0291 vs. control, d = 3.207). Adult male GD offspring showed a deficiency in short-term memory (P = 0.017, d = 1.795). We found an increase in ROS and lipid peroxidation, a disruption in the glutathione status, and decreased activity of catalase and superoxide dismutase (P < 0.05 vs. control, d > 1.0), in the cerebral cortex and hippocampus of male and female GD offspring. GD altered metabolism; male offspring of both ages and adult females showed a high level of triglycerides and a lower level of high-density lipoprotein-cholesterol (P < 0.05 vs. control, d > 1.0). Young and adult female offspring displayed higher insulin levels (P < 0.05, d > 1.0). These results suggest that gestational diabetes modifies oxidative stress and cognitive behavior in an age- and sex-dependent manner.
format Online
Article
Text
id pubmed-7071266
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-70712662020-03-19 Gestational Diabetes Triggers Oxidative Stress in Hippocampus and Cerebral Cortex and Cognitive Behavior Modifications in Rat Offspring: Age- and Sex-Dependent Effects Huerta-Cervantes, Maribel Peña-Montes, Donovan J. Montoya-Pérez, Rocío Trujillo, Xóchitl Huerta, Miguel López-Vázquez, Miguel Ángel Olvera-Cortés, María Esther Saavedra-Molina, Alfredo Nutrients Article Gestational diabetes (GD) has been linked with an increased risk of developing metabolic disorders and behavioral abnormalities in the offspring. Oxidative stress is strongly associated with neurodegeneration and cognitive disruption. In the offspring brains in a GD experimental rat model, increased oxidative stress in the prenatal and postnatal stages was reported. However, long-term alterations to offspring behavior and oxidative stress, caused by changes in the cerebral cortex and hippocampus, remain unclear. In this study, we evaluated the effect of GD on young and adult male and female rat offspring in metabolic parameters, cognitive behavior, and oxidative stress. GD was induced using streptozotocin in dams. Next, the offspring were evaluated at two and six months of age. Anxiety-like behavior was evaluated using the elevated plus maze and open field maze; spatial learning and short-term memory were evaluated using the Morris water maze and radial maze, respectively. We determined oxidative stress biomarkers (reactive oxygen species (ROS), lipid peroxidation and glutathione status) and antioxidant enzymes (superoxide dismutase and catalase) in the brain of offspring. We observed that male GD offspring showed a reduced level of anxiety at both ages as they spent less time in the closed arms of the elevated plus maze at adult age ((P = 0.019, d = 1.083 ( size effect)) and spent more time in the open area of an open field (P = 0.0412, d = 0.743) when young and adult age (P = 0.018, d = 0.65). Adult female GD offspring showed a reduced level of anxiety (P = 0.036; d = 0.966), and young female GD offspring showed a deficiency in spatial learning (P = 0.0291 vs. control, d = 3.207). Adult male GD offspring showed a deficiency in short-term memory (P = 0.017, d = 1.795). We found an increase in ROS and lipid peroxidation, a disruption in the glutathione status, and decreased activity of catalase and superoxide dismutase (P < 0.05 vs. control, d > 1.0), in the cerebral cortex and hippocampus of male and female GD offspring. GD altered metabolism; male offspring of both ages and adult females showed a high level of triglycerides and a lower level of high-density lipoprotein-cholesterol (P < 0.05 vs. control, d > 1.0). Young and adult female offspring displayed higher insulin levels (P < 0.05, d > 1.0). These results suggest that gestational diabetes modifies oxidative stress and cognitive behavior in an age- and sex-dependent manner. MDPI 2020-01-31 /pmc/articles/PMC7071266/ /pubmed/32023917 http://dx.doi.org/10.3390/nu12020376 Text en © 2020 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 Article
Huerta-Cervantes, Maribel
Peña-Montes, Donovan J.
Montoya-Pérez, Rocío
Trujillo, Xóchitl
Huerta, Miguel
López-Vázquez, Miguel Ángel
Olvera-Cortés, María Esther
Saavedra-Molina, Alfredo
Gestational Diabetes Triggers Oxidative Stress in Hippocampus and Cerebral Cortex and Cognitive Behavior Modifications in Rat Offspring: Age- and Sex-Dependent Effects
title Gestational Diabetes Triggers Oxidative Stress in Hippocampus and Cerebral Cortex and Cognitive Behavior Modifications in Rat Offspring: Age- and Sex-Dependent Effects
title_full Gestational Diabetes Triggers Oxidative Stress in Hippocampus and Cerebral Cortex and Cognitive Behavior Modifications in Rat Offspring: Age- and Sex-Dependent Effects
title_fullStr Gestational Diabetes Triggers Oxidative Stress in Hippocampus and Cerebral Cortex and Cognitive Behavior Modifications in Rat Offspring: Age- and Sex-Dependent Effects
title_full_unstemmed Gestational Diabetes Triggers Oxidative Stress in Hippocampus and Cerebral Cortex and Cognitive Behavior Modifications in Rat Offspring: Age- and Sex-Dependent Effects
title_short Gestational Diabetes Triggers Oxidative Stress in Hippocampus and Cerebral Cortex and Cognitive Behavior Modifications in Rat Offspring: Age- and Sex-Dependent Effects
title_sort gestational diabetes triggers oxidative stress in hippocampus and cerebral cortex and cognitive behavior modifications in rat offspring: age- and sex-dependent effects
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7071266/
https://www.ncbi.nlm.nih.gov/pubmed/32023917
http://dx.doi.org/10.3390/nu12020376
work_keys_str_mv AT huertacervantesmaribel gestationaldiabetestriggersoxidativestressinhippocampusandcerebralcortexandcognitivebehaviormodificationsinratoffspringageandsexdependenteffects
AT penamontesdonovanj gestationaldiabetestriggersoxidativestressinhippocampusandcerebralcortexandcognitivebehaviormodificationsinratoffspringageandsexdependenteffects
AT montoyaperezrocio gestationaldiabetestriggersoxidativestressinhippocampusandcerebralcortexandcognitivebehaviormodificationsinratoffspringageandsexdependenteffects
AT trujilloxochitl gestationaldiabetestriggersoxidativestressinhippocampusandcerebralcortexandcognitivebehaviormodificationsinratoffspringageandsexdependenteffects
AT huertamiguel gestationaldiabetestriggersoxidativestressinhippocampusandcerebralcortexandcognitivebehaviormodificationsinratoffspringageandsexdependenteffects
AT lopezvazquezmiguelangel gestationaldiabetestriggersoxidativestressinhippocampusandcerebralcortexandcognitivebehaviormodificationsinratoffspringageandsexdependenteffects
AT olveracortesmariaesther gestationaldiabetestriggersoxidativestressinhippocampusandcerebralcortexandcognitivebehaviormodificationsinratoffspringageandsexdependenteffects
AT saavedramolinaalfredo gestationaldiabetestriggersoxidativestressinhippocampusandcerebralcortexandcognitivebehaviormodificationsinratoffspringageandsexdependenteffects