Hippocampal NMDAR-Wnt-Catenin signaling disrupted with cognitive deficits in adolescent offspring exposed to prenatal hypoxia

Wei, Bin; Li, Lingjun; He, Axin; Zhang, Yingying; Sun, Miao; Xu, Zhice

doi:10.1016/j.brainres.2015.11.041

Cited by 26 publications

(25 citation statements)

References 43 publications

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“…Prenatal hypoxia affected the fetal brain and kidney development as well as learning and memory in the male offspring. 4,16 Hypoxia during pregnancy, like exposure to nicotine and malnutrition, could cause adult diseases in fetal origins. [17][18][19] In the present study hypoxia caused in utero growth restriction as evidenced by lower birth weight and brain weight.…”

Section: Discussion and Summarymentioning

confidence: 99%

“…Damage to the MCA could cause stroke and other brain diseases . Recent progress has been made in demonstrating that hypoxia during pregnancy can cause vascular diseases and damaged learning/memory ability in the offspring . However, it is still unknown whether cerebral vessels would be influenced by prenatal hypoxia.…”

Section: Introductionmentioning

confidence: 99%

“…1,2 Recent progress has been made in demonstrating that hypoxia during pregnancy can cause vascular diseases and damaged learning/memory ability in the offspring. [3][4][5] However, it is still unknown whether cerebral vessels would be influenced by prenatal hypoxia. It is worthwhile to investigate whether and how prenatal hypoxia affects central vascular systems.…”

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confidence: 99%

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Prenatal Hypoxia Induced Dysfunction in Cerebral Arteries of Offspring Rats

Tang

Chen

et al. 2017

JAHA

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BackgroundHypoxia during pregnancy could cause abnormal development and lead to increased risks of vascular diseases in adults. This study determined angiotensin II (AII)‐mediated vascular dysfunction in offspring middle cerebral arteries (MCA).Methods and ResultsPregnant rats were subjected to hypoxia. Vascular tension in offspring MCA by AII with or without inhibitors, calcium channel activities, and endoplasmic reticulum calcium stores were tested. Whole‐cell patch clamping was used to investigate voltage‐dependent calcium channel currents. mRNA expression was tested using quantitative real‐time polymerase chain reaction. AII‐mediated MCA constriction was greater in male offspring exposed to prenatal hypoxia. AT1 and AT2 receptors were involved in the altered AII‐mediated vasoconstriction. Prenatal hypoxia increased baseline activities of L‐type calcium channel currents in MCA smooth muscle cells. However, calcium currents stimulated by AII were not significantly changed, whereas nifedipine inhibited AII‐mediated vasoconstrictions in the MCA. Activities of IP 3/ryanodine receptor–operated calcium channels, endoplasmic reticulum calcium stores, and sarcoendoplasmic reticulum membrane Ca2+‐ATPase were increased. Prenatal hypoxia also caused dysfunction of vasodilatation via the endothelium NO synthase. The mRNA expressions of AT1A, AT1B, AT2R, Cav1.2α1C, Cav3.2α1H, and ryanodine receptor RyR2 were increased in the prenatal‐hypoxia group.ConclusionsHypoxia in pregnancy could induce dysfunction in both contraction and dilation in the offspring MCA. AII‐increased constriction in the prenatal‐hypoxia group was not mainly dependent on the L‐type and T‐type calcium channels; it might predominantly rely on the AII receptors, IP 3/ryanodine receptors, and the endoplasmic reticulum calcium store as well as calcium ATPase.

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Section: Discussion and Summarymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Prenatal Hypoxia Induced Dysfunction in Cerebral Arteries of Offspring Rats

Tang

Chen

et al. 2017

JAHA

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“…The membranes were incubated with antibodies directed against phospho‐Akt and Akt (Cell Signaling, Boston, USA catalogue numbers 9271 and 9272, respectively); phospho‐IRS‐1 and IRS‐1 (Cell Signaling, Boston, USA catalogue numbers 3193 and 2382, respectively); and phospho‐GSK‐3β and GSK‐3β (Cell Signaling, Boston, USA catalogue numbers 9322 and 9315, respectively). The protocol was carried out as previously reported …”

Section: Methodsmentioning

confidence: 99%

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

Zhang

Zhu

Zhang

et al. 2018

Molecular Nutrition Food Res

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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.

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“…Our laboratory reported that Wnt/β‐catenin was decreased in the brain of the adolescence offspring exposed to prenatal hypoxia, with long‐term effects on hippocampal neurogenesis and functions. However, why prenatal hypoxia could result in decreased Wnt/β‐catenin signals needs further investigation …”

Section: Introductionmentioning

confidence: 99%

Methylation‐reprogrammed Wnt/β‐catenin signalling mediated prenatal hypoxia‐induced brain injury in foetal and offspring rats

Zhang

Wei

et al. 2018

J Cellular Molecular Medi

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Prenatal hypoxia (PH) is a common pregnancy complication, harmful to brain development. This study investigated whether and how PH affected Wnt pathway in the brain. Pregnant rats were exposed to hypoxia (10.5% O2) or normoxia (21% O2; Control). Foetal brain weight and body weight were decreased in the PH group, the ratio of brain weight to body weight was increased significantly. Prenatal hypoxia increased mRNA expression of Wnt3a, Wnt7a, Wnt7b and Fzd4, but not Lrp6. Activated β‐catenin protein and Fosl1 expression were also significantly up‐regulated. Increased Hif1a expression was found in the PH group associated with the higher Wnt signalling. Among 5 members of the Sfrp family, Sfrp4 was down‐regulated. In the methylation‐regulating genes, higher mRNA expressions of Dnmt1 and Dnmt3b were found in the PH group. Sodium bisulphite and sequencing revealed hyper‐methylation in the promoter region of Sfrp4 gene in the foetal brain, accounting for its decreased expression and contributing to the activation of the Wnt‐Catenin signalling. The study of PC12 cells treated with 5‐aza further approved that decreased methylation could result in the higher Sfrp4 expression. In the offspring hippocampus, protein levels of Hif1a and mRNA expression of Sfrp4 were unchanged, whereas Wnt signal pathway was inhibited. The data demonstrated that PH activated the Wnt pathway in the foetal brain, related to the hyper‐methylation of Sfrp4 as well as Hif1a signalling. Activated Wnt signalling might play acute protective roles to the foetal brain in response to hypoxia, also would result in disadvantageous influence on the offspring in long‐term.

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Hippocampal NMDAR-Wnt-Catenin signaling disrupted with cognitive deficits in adolescent offspring exposed to prenatal hypoxia

Cited by 26 publications

References 43 publications

Prenatal Hypoxia Induced Dysfunction in Cerebral Arteries of Offspring Rats

Prenatal Hypoxia Induced Dysfunction in Cerebral Arteries of Offspring Rats

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

Methylation‐reprogrammed Wnt/β‐catenin signalling mediated prenatal hypoxia‐induced brain injury in foetal and offspring rats

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