Effects of prenatal protein malnutrition on the hippocampal formation

Morgane, Peter J.; Mokler, David J.; Galler, Janina R.

doi:10.1016/s0149-7634(02)00012-x

Cited by 348 publications

(321 citation statements)

References 43 publications

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“…4a). We focused on the hippocampus (for dissection details, see Supplementary Methods) and the GABAergic and serotoninergic (5-HT) neurotransmitter systems in light of their established key roles in mediating anxiogenic behaviour 37,38 and sensitivity to earlylife manipulations [39][40][41] . Quantitative PCR (see Supplementary Methods) revealed a highly specific pattern of hippocampal gene expression changes, with significant reductions in expression of the GABAAa3 receptor subunit and 5-HT 2A receptor message in the Igf2-P0 KO mice (Fig.…”

Section: Article Nature Communications | Doi: 101038/ncomms3311mentioning

confidence: 91%

Placental programming of anxiety in adulthood revealed by Igf2-null models

et al. 2013

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Section: Article Nature Communications | Doi: 101038/ncomms3311mentioning

confidence: 91%

Placental programming of anxiety in adulthood revealed by Igf2-null models

et al. 2013

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“…In keeping with this notion, most studies of the mechanisms underlying BW differences between MZ twins have focused on the placenta as the chief determinant of the in utero environment, linking withintwin differences in prenatal growth to inequitable access to placental tissue (35). The capacity of placental mechanisms for BW variation to also impact brain development has been established through experimental modification of effective placental transfer in animal models of placental insufficiency (1) and maternal undernutrition (36,37). In humans, ultrasonographic markers of placental insufficiency have been shown to predict neurobehavioral outcomes during fetal and early postnatal life (38,39).…”

Section: Modeling Prenatal Environmental Influences On Brain Developmentmentioning

confidence: 99%

Prenatal growth in humans and postnatal brain maturation into late adolescence

Raznahan

Greenstein²,

Lee³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

177

179

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Prenatal life encompasses a critical phase of human brain development, but neurodevelopmental consequences of normative differences in prenatal growth among full-term pregnancies remain largely uncharted. Here, we combine the power of a withinmonozygotic twin study design with longitudinal neuroimaging methods that parse dissociable components of structural brain development between ages 3 and 30 y, to show that subtle variations of the in utero environment, as indexed by mild birth weight (BW) variation within monozygotic pairs, are accompanied by statistically significant (i) differences in postnatal intelligence quotient (IQ) and (ii) alterations of brain anatomy that persist at least into late adolescence. Greater BW within the normal range confers a sustained and generalized increase in brain volume, which in the cortical sheet, is specifically driven by altered surface area rather than cortical thickness. Surface area is maximally sensitive to BW variation within cortical regions implicated in the biology of several mental disorders, the risk for which is modified by normative BW variation. We complement this near-experimental test of prenatal environmental influences on human brain development by replicating anatomical findings in dizygotic twins and unrelated singletons. Thus, using over 1,000 brain scans, across three independent samples, we link subtle differences in prenatal growth, within ranges seen among the majority of human pregnancies, to protracted surface area alterations, that preferentially impact later-maturing associative cortices important for higher cognition. By mapping the sensitivity of postnatal human brain development to prenatal influences, our findings underline the potency of in utero life in shaping postnatal outcomes of neuroscientific and public health importance.P renatal life encompasses a foundational and universally critical phase of human brain development. Consequently, research aimed at understanding how prenatal influences play out in later life cannot only illuminate mechanisms of fundamental importance to basic developmental neuroscience, but may also have public health implications.Exquisite sensitivity of the developing brain to prenatal environmental insults has been well established through experimental animal models (1). In humans, where experimental approaches are not feasible, numerous observational studies have linked frank insults during prenatal life [as indexed by premature delivery (2); abnormally low birth weight for gestational age (3); and maternal exposure to radiation (4) or starvation (5)], to altered postnatal brain development. However, by virtue of their relative rarity, such frank prenatal insults may be less impactful at the population level than more subtle variations of the in utero environment occurring among the uncomplicated pregnancies from which most people are born (6). Evidence that subtle alterations of the prenatal environment may have meaningful consequences for postnatal development in humans can be found in large-scale epidemiolog...

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“…Thus, extrapolation from mouse to man may not be possible on specific days of pregnancy, but can be construed from prenatal and postnatal peaks of neurogenesis, gliogenesis and neuron/glia differentiation and migration (Susser et al 1999). The choice of postnatal days 35 and 56 in our studies are based on a large group of supportive literature (Avishai-Eliner et al 2002;Boksa et al 2003;Kaufmann, 2000;Morgane et al 2002;Romijn et al 1991;Spear, 2000;Susser et al 1999) denoting E0-E10 in rodents as equal to first trimester in humans, E11-E19 as equal to 2 nd trimester, P0-P7 as equal to third trimester (Morgane et al 2002;Stead et al 2006), P35 as equal to adolescence (Spear, 2000) and P56 as equal to early adulthood (Spear, 2000).…”

Section: Animals and Infectionmentioning

confidence: 99%

Viral regulation of aquaporin 4, connexin 43, microcephalin and nucleolin

Fatemi¹,

Folsom²,

Reutiman³

et al. 2008

Schizophrenia Research

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The current study investigated whether human influenza viral infection in midpregnancy leads to alterations in proteins involved in brain development. Human influenza viral infection was administered to E9 pregnant Balb/c mice. Brains of control and virally exposed littermates were subjected to microarray analysis, SDS-PAGE and western blotting at three postnatal stages. Microarray analysis of virally-exposed mouse brains showed significant, two-fold change in expression of multiple genes in both neocortex and cerebellum when compared to sham-infected controls. Levels of mRNA and protein levels of four selected genes were examined in brains of exposed mice. Nucleolin mRNA was significantly decreased in day 0 and day 35 neocortex and significantly increased in day 35 cerebellum. Protein levels were significantly upregulated at days 35 and 56 in neocortex and at day 56 in cerebellum. Connexin 43 protein levels were significantly decreased at day 56 in neocortex. Aquaporin 4 mRNA was significantly decreased in day 0 neocortex. Aquaporin 4 protein levels decreased in neocortex significantly at day 35. Finally, microcephalin mRNA was significantly decreased in day 56 neocortex and protein levels were significantly decreased at 56 cerebellum. These data suggest that influenza viral infection in midpregnancy in mice leads to long term changes in brain markers for enhanced ribosome genesis (nucleolin), increased production of immature neurons (microcephalin), and abnormal glial-neuronal communication (connexin 43 and aquaporin 4).

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Effects of prenatal protein malnutrition on the hippocampal formation

Cited by 348 publications

References 43 publications

Placental programming of anxiety in adulthood revealed by Igf2-null models

Placental programming of anxiety in adulthood revealed by Igf2-null models

Prenatal growth in humans and postnatal brain maturation into late adolescence

Viral regulation of aquaporin 4, connexin 43, microcephalin and nucleolin

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