Prenatal high sucrose intake affected learning and memory of aged rat offspring with abnormal oxidative stress and NMDARs/Wnt signaling in the hippocampus

Zhu

Molecular Nutrition Food Res

et al. 2018

Self Cite

Both prenatal and prenatal-plus-postnatal high sucrose exposure substantially affect biological functions related to insulin homeostasis. IRS-1(S612) protein phosphorylation appears to be a part of the molecular mechanism underlying these effects. These results add to the understanding of how high sucrose intake contributes to insulin resistance and diabetes pathogenesis and how postnatal nutrition and lifestyle may mitigate detrimental prenatal exposures.

Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Synergetic Effects of Prenatal and Postnatal High Sucrose Intake on Glucose Tolerance and Hepatic Insulin Resistance in Rat Offspring

Zhu

Molecular Nutrition Food Res

et al. 2018

Self Cite

“…Conversely, certain types of perinatal compromise have been associated with decreased activity of the GRIN2B gene and subsequent deficits in hippocampal learning, which highlights the balancing role of GRIN2B expression for optimal neurodevelopment. In particular, high‐fat and high‐sucrose maternal diets in rats have both been shown to increase and decrease the expression of GluN2B in the amygdala and hippocampus, respectively, with an anxious‐phenotype being displayed during adolescence and long‐lasting cognitive deficits present in the F1 offspring . Prenatal hypoxia, a common consequence of intrauterine growth restriction, is also associated with decreased expression of GluN2B in the hippocampus and subsequent impaired cognitive ability as indicated by diminished performance in the Morris water maze of 6‐week‐old rats .…”

Section: Dysregulation Of Gabaergic and Glutamatergic Pathways In Dismentioning

confidence: 99%

Perinatal compromise contributes to programming of GABAergic and glutamatergic systems leading to long‐term effects on offspring behaviour

Shaw

Crombie

Zakár

et al. 2019

J Neuroendocrinology

Extensive evidence now shows that adversity during the perinatal period is a significant risk factor for the development of neurodevelopmental disorders long after the causative event. Despite stemming from a variety of causes, perinatal compromise appears to have similar effects on the developing brain, thereby resulting in behavioural disorders of a similar nature. These behavioural disorders occur in a sex‐dependent manner, with males affected more by externalising behaviours such as attention deficit hyperactivity disorder (ADHD) and females by internalising behaviours such as anxiety. Regardless of the causative event or the sex of the offspring, these disorders may begin in childhood or adolescence but extend into adulthood. A mechanism by which adverse events in the perinatal period impact later in life behaviour has been shown to be the changing epigenetic landscape. Methylation of the GAD1/GAD67 gene, which encodes the key glutamate‐to‐GABA‐synthesising enzyme glutamate decarboxylase 1, resulting in increased levels of glutamate, is one epigenetic mechanism that may account for a tendency towards excitation in disorders such as ADHD. Exposure of the fetus or the neonate to high levels of cortisol may be the mediator between perinatal compromise and poor behavioural outcomes because evidence suggests that increased glucocorticoid exposure triggers widespread changes in the epigenetic landscape. This review summarises the current evidence and recent literature about the impact of various perinatal insults on the epigenome and the common mechanisms that may explain the similarity of behavioural outcomes occurring following diverse perinatal compromise.

“…Experimental investigations in animals indicated that uncontrolled diabetes mellitus was associated with morphological and functional alterations in the brain [12][13][14]. Hippocampus, a structure critical to cognitive processes, has been shown to undergo apoptotic cell death when subjected to hyperglycemic insult [15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Intergenerational neurocognitive effects of intrauterine hyperglycemia on male offspring

Zou¹,

Ren²,

Junyu³

et al. 2020

Preprint

Background Studies on human and animals suggest associations between gestational diabetes mellitus (GDM) with increased susceptibility to develop neurological disorders in offspring. However, researches have focused on the neurodevelopment consequences of the first filial (F1) offspring. We hypothesize that the intrauterine hyperglycemia exposure will alter epigenetic reprogramming in F1 sperm, and carry risks of passing on molecular defects to the second filial (F2). Results We found that intrauterine hyperglycemia exposure resulted in memory impairment in both F1 and F2 males from the F1-GDM male offspring. Transcriptome profiling of F1 and F2 hippocampi revealed that differentially expressed genes were enriched in learning, memory, cognition, neurotransmission, synaptic plasticity, and postsynaptic specialization. Again, enrichment curves computed by Gene set enrichment analysis (GSEA) of F1 hippocampi were highly consistent with F2. Interestingly, combined analysis of F1 sperm methylome and gene expression of F2 hippocampi screened out several hypermethylation-low expression genes which are associated with abnormal central nervous system development (particularly synapse development and homeostasis), such as Camk2b, Dlgap1, Wnt5a, Tubb2b and so on. Conclusions These findings implicate that the male germ line is a major player in transgenerational phenotypic transmission. Taken together, our results for the first time suggest that intrauterine hyperglycemia leads to transgenerational cognitive impairment, and, sperm methylome is a potential epigenetic mechanism for the effects of GDM.