Severe Uncontrolled Maternal Hyperglycemia Induces Microsomia and Neurodevelopment Delay Accompanied by Apoptosis, Cellular Survival, and Neuroinflammatory Deregulation in Rat Offspring Hippocampus

Piazza, Francele Valente; Segabinazi, Ethiane; Meireles, André Luís Ferreira de; Mega, Filipe; Spindler, Christiano; Augustin, Otávio Américo; Salvalaggio, Gabriela dos Santos; Achaval, Matilde; Kruse, María Sol; Coirini, Héctor; Marcuzzo, Simone

doi:10.1007/s10571-019-00658-8

Cited by 31 publications

(18 citation statements)

References 59 publications

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“…Our results showed that the body weight of the offspring of diabetic dams is lower than that observed in offspring of control dams as previously reported by Piazza et al 21 .…”

Section: Recognition Index (%)supporting

confidence: 91%

Effect of ginger on hyperglycemia induced by streptozotocin in pregnant rats and postnatal neurodevelopment of their offspring

Raouia¹,

Habiba²,

Tahraoui³

2020

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This study was performed to investigate the consequences of severe maternal hyperglycemia induced by streptozotocin in Wistar rats on postnatal development of offspring. Besides, the ability of a ginger extract to restore glycemic balance in dams and prevent the appearance of disorders in offspring. Diabetes was induced in dams before pregnancy by a single injection of streptozotocin at a dose of 50 mg / kg. Ginger was orally administered from the fourteenth (14th) to the nineteenth (19th) day of pregnancy. Two tests before and after weaning were performed to monitor the offspring development. Our study clearly showed that treatment of diabetic pregnant rats with a ginger extract lowers blood glucose levels and help prevent disorders in offspring.

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“…Our results showed that the body weight of the offspring of diabetic dams is lower than that observed in offspring of control dams as previously reported by Piazza et al 21 .…”

Section: Recognition Index (%)supporting

confidence: 91%

Effect of ginger on hyperglycemia induced by streptozotocin in pregnant rats and postnatal neurodevelopment of their offspring

Raouia¹,

Habiba²,

Tahraoui³

2020

actapharm

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“…Our results only indicated a lower body weight at birth (microsomia) in male offspring of GD rats, and this change remained during the weaning, juvenile, and adult stages. This weight reduction at birth could be due to the high blood glucose concentration in the intrauterine milieu during gestational diabetes, since it was reported to induce pancreatic hypertrophy due to the over-stimulation of pancreatic β cells, preventing the secretion of insulin and decreasing anabolism and, subsequently, neonatal microsomia [3,[34][35][36], this results are according with [37]. The female offspring of GD showed a lower body weight only during weaning, without changes at birth or juvenile and adult stages.…”

Section: Discussionmentioning

confidence: 95%

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

et al. 2020

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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.

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“…1). Rodent models on high fat diet (HFD) or with hyperglycemia have been used in this context supporting a role of the intrauterine environment [20,[60][61][62][63]. Offspring to pregnant dams of these models display altered behaviors such as hyperactivity, reduced sociability and anxious and depressive-like behaviors [20].…”

Section: Brief Overview Of Potential Pathways and Mechanismsmentioning

confidence: 99%

“…Low-grade inflammation is commonly seen in obese and/or diabetic pregnant mothers. Pro-inflammatory cytokines passing the placenta to the fetus exposing the offspring brain during gestation are known to influence the development of neural pathways regulating behavior, such as the hypothalamic-pituitary-adrenal (HPA) axis, and serotonergic and dopaminergic systems and BDNF levels [60]. IL-6 is an early key pro-inflammatory cytokine.…”

Section: Immune Activity Effectsmentioning

confidence: 99%

“…Changes in development of the serotonergic system and in serotonin signaling have been observed in rodent and nonhuman primate models owing to maternal inflammation or a HFD, leading to increased risk for behavioral abnormalities in offspring [133][134][135]. Altered dopamine sensitivity, as well as abnormal dopamine and BDNF expression are also documented in rats of mothers fed with HFD [60,136,137]. Moreover, maternal inflammation, modeled with IL-6 and leptin, has been associated with dopamine signaling in offspring [138].…”

Section: Serotonergic and Dopaminergic System Effectsmentioning

confidence: 99%

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Relationship of prenatal maternal obesity and diabetes to offspring neurodevelopmental and psychiatric disorders: a narrative review

et al. 2020

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Obesity and diabetes is a worldwide public health problem among women of reproductive age. This narrative review highlights recent epidemiological studies regarding associations of maternal obesity and diabetes with neurodevelopmental and psychiatric disorders in offspring, and provides an overview of plausible underlying mechanisms and challenges for future human studies. A comprehensive search strategy selected terms that corresponded to the domains of interest (maternal obesity, different types of diabetes, offspring cognitive functions and neuropsychiatric disorders). The databases searched for articles published between January 2010 and April 2019 were PubMed, Web of Science and CINAHL. Evidence from epidemiological studies strongly suggests that maternal pre-pregnancy obesity is associated with increased risks for autism spectrum disorder, attention-deficit hyperactivity disorder and cognitive dysfunction with modest effect sizes, and that maternal diabetes is associated with the risk of the former two disorders. The influence of maternal obesity on other psychiatric disorders is less well studied, but there are reports of associations with increased risks for offspring depression, anxiety, schizophrenia and eating disorders, at modest effect sizes. It remains unclear whether these associations are due to intrauterine mechanisms or explained by confounding family-based sociodemographic, lifestyle and genetic factors. The plausible underlying mechanisms have been explored primarily in animal models, and are yet to be further investigated in human studies.

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Severe Uncontrolled Maternal Hyperglycemia Induces Microsomia and Neurodevelopment Delay Accompanied by Apoptosis, Cellular Survival, and Neuroinflammatory Deregulation in Rat Offspring Hippocampus

Cited by 31 publications

References 59 publications

Effect of ginger on hyperglycemia induced by streptozotocin in pregnant rats and postnatal neurodevelopment of their offspring

Effect of ginger on hyperglycemia induced by streptozotocin in pregnant rats and postnatal neurodevelopment of their offspring

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

Relationship of prenatal maternal obesity and diabetes to offspring neurodevelopmental and psychiatric disorders: a narrative review

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