Growth restriction, leptin, and the programming of adult behavior in mice

Meyer, Lauritz R.; Zhu, Vivian; Miller, Alise K.; Roghair, Robert D.

doi:10.1016/j.bbr.2014.08.054

Cited by 25 publications

(22 citation statements)

References 32 publications

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“…Leptin is believed to impact fetal organ growth, including the brain, appetite regulation, and cognition during early development (Briffa et al 2015). Some authors have suggested that leptin replacement in early life may improve long-term metabolic and behavioral outcomes (Meyer et al 2014; Chen et al 2011). …”

Section: Long-term Outcomes Of Children Born To Obese Mothersmentioning

confidence: 99%

Effects of maternal obesity on placental function and fetal development

2017

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Obesity has reached epidemic proportions and pregnancies in obese mothers have increased risk for complications including gestational diabetes, hypertensive disorders, preterm birth and caesarian section. Children born to obese mothers are at increased risk of obesity and metabolic disease and are susceptible to develop neuropsychiatric and cognitive disorders. Changes in placental function not only play a critical role in the development of pregnancy complications but may also be involved in linking maternal obesity to long-term health risks in the infant. Maternal adipokines i.e., interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-α), leptin and adiponectin link maternal nutritional status and adipose tissue metabolism to placental function. Adipokines and metabolic hormones have direct impact on placental function by modulating placental nutrient transport. Nutrient delivery to the fetus is regulated by a complex interaction between insulin signaling, cytokine profile and insulin responsiveness, which is modulated by adiponectin and IL-1β. In addition, obese pregnant women are at risk for hypertension and preeclampsia with reduced placental vascularity and blood flow, which would restrict placental nutrient delivery to the developing fetus. These sometimes opposing signals regulating placental function may contribute to the diversity of short and long-term outcomes observed in pregnant obese women. This review focuses on the changes in adipokines and obesity-related metabolic hormones, how these factors influence placental function and fetal development to contribute to long-term metabolic and behavioral consequences of children born to obese mothers.

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Section: Long-term Outcomes Of Children Born To Obese Mothersmentioning

confidence: 99%

Effects of maternal obesity on placental function and fetal development

2017

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“…During the appropriate critical period, it has been demonstrated that precise correction of growth restriction-induced neonatal leptin deficiency with neonatal leptin supplementation (0.08 mg/kg/d) blocks the programming of stress-related hypertension, elicits neurotrophic effects on the hypothalamus, and improves both learning and social interaction (Erkonen et al, 2011; Meyer et al, 2014). To further clarify the effect of isolated leptin deficiency during development, a leptin antagonist was administered to well grown neonatal mice, and adult phenotypes were compared four months after the treatment concluded.…”

Section: Variation In Intrauterine and Neonatal Developmentmentioning

confidence: 99%

Challenges and opportunities in developmental integrative physiology

Mueller

Eme

Burggren

et al. 2015

Comparative Biochemistry and Physiology Part A: Molecular &

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This review explores challenges and opportunities in developmental physiology outlined by a symposium at the 2014 American Physiological Society Intersociety Meeting: Comparative Approaches to Grand Challenges in Physiology. Across animal taxa, adverse embryonic/fetal environmental conditions can alter morphological and physiological phenotypes in juveniles or adults, and capacities for developmental plasticity are common phenomena. Human neonates with body sizes at the extremes of perinatal growth are at an increased risk of adult disease, particularly hypertension and cardiovascular disease. There are many rewarding areas of current and future research in comparative developmental physiology. We present key mechanisms, models, and experimental designs that can be used across taxa to investigate patterns in, and implications of, the development of animal phenotypes. Intraspecific variation in the timing of developmental events can be increased through developmental plasticity (heterokairy), and could provide the raw material for selection to produce heterochrony — an evolutionary change in the timing of developmental events. Epigenetics and critical windows research recognizes that in ovo or fetal development represent a vulnerable period in the life history of an animal, when the developing organism may be unable to actively mitigate environmental perturbations. ‘Critical windows’ are periods of susceptibility or vulnerability to environmental or maternal challenges, periods when recovery from challenge is possible, and periods when the phenotype or epigenome has been altered. Developmental plasticity may allow survival in an altered environment, but it also has possible long-term consequences for the animal. “Catch-up growth” in humans after the critical perinatal window has closed elicits adult obesity and exacerbates a programmed hypertensive phenotype (one of many examples of “fetal programing”). Grand challenges for developmental physiology include integrating variation in developmental timing within and across generations, applying multiple stressor dosages and stressor exposure at different developmental timepoints, assessment of epigenetic and parental influences, developing new animal models and techniques, and assessing and implementing these designs and models in human health and development.

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“…Social interaction was assessed using a tripartite chamber as previously described in adult mice who received perinatal sertraline and saline injections [22]. The amount of time spent in each chamber was measured, along with the amount of time spent interacting (sniffing) with the stranger mouse versus the empty enclosure.…”

Section: Methodsmentioning

confidence: 99%

Perinatal SSRI exposure permanently alters cerebral serotonin receptor mRNA in mice but does not impact adult behaviors

Meyer

Dexter

et al. 2017

The Journal of Maternal-Fetal & Neonatal Medicine

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Purpose: Associations have been made between maternal selective serotonin reuptake inhibitor (SSRI) use during pregnancy and altered behavior in offspring, including an increased risk of autism. Given the important role serotonin plays in behavior, we hypothesized SSRI exposure in the perinatal period would alter central serotonin receptor expression and program adult behaviors in mice. Methods: Female mice were injected with sertraline or saline throughout pregnancy. Offspring continued to receive injections on postnatal days 1–14, a time period in mice similar to the third trimester in human pregnancy. Adult offspring underwent behavioral testing and serotonin receptor mRNA levels were quantified. Results: Compared to controls, SSRI exposed mice did not have a reduction in social interactions, spatial learning, or exploratory behavior. As adults, sertraline exposed mice had significantly increased mRNA levels of multiple 5-HT receptors, serotonin transporter (5-HTT), and tryptophan hydroxylase isoform 2 in the cerebral cortex. Conclusion: Although no behavioral phenotype was observed, SSRI exposure in the perinatal period permanently alters cerebral receptor mRNA levels. We speculate these shifts in mRNA expression provide important compensation during SSRI exposure. Further pre-clinical and clinical investigation into additional serotonin-regulated phenotypes is necessary to further assess the long-term implications of perinatal SSRI exposure.

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Growth restriction, leptin, and the programming of adult behavior in mice

Cited by 25 publications

References 32 publications

Effects of maternal obesity on placental function and fetal development

Effects of maternal obesity on placental function and fetal development

Challenges and opportunities in developmental integrative physiology

Perinatal SSRI exposure permanently alters cerebral serotonin receptor mRNA in mice but does not impact adult behaviors

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