Mouse maternal protein restriction during preimplantation alone permanently alters brain neuron proportion and adult short-term memory

Joanna M Gould, Phoebe J Smith, Chris J Airey, Emily J Mort, Lauren E Airey, Frazer D M Warricker, Jennifer E Pearson-Farr, Eleanor C Weston, Philippa J W Gould, Oliver G Semmence, Katie L Restall, Jennifer A Watts, Patrick C McHugh, Stephanie J Smith, Jennifer M Dewing, Tom P Fleming, Sandrine Willaime-Morawek

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9 Citations (Scopus)

Abstract

Maternal protein malnutrition throughout pregnancy and lactation compromises brain development in late gestation and after birth, affecting structural, biochemical, and pathway dynamics with lasting consequences for motor and cognitive function. However, the importance of nutrition during the preimplantation period for brain development is unknown. We have previously shown that maternal low-protein diet (LPD) confined to the preimplantation period (Emb-LPD) in mice, with normal nutrition thereafter, is sufficient to induce cardiometabolic and locomotory behavioral abnormalities in adult offspring. Here, using a range of in vivo and in vitro techniques, we report that Emb-LPD and sustained LPD reduce neural stem cell (NSC) and progenitor cell numbers at E12.5, E14.5, and E17.5 through suppressed proliferation rates in both ganglionic eminences and cortex of the fetal brain. Moreover, Emb-LPD causes remaining NSCs to up-regulate the neuronal differentiation rate beyond control levels, whereas in LPD, apoptosis increases to possibly temper neuron formation. Furthermore, Emb-LPD adult offspring maintain the increase in neuron proportion in the cortex, display increased cortex thickness, and exhibit short-term memory deficit analyzed by the novel-object recognition assay. Last, we identify altered expression of fragile X family genes as a potential molecular mechanism for adverse programming of brain development. Collectively, these data demonstrate that poor maternal nutrition from conception is sufficient to cause abnormal brain development and adult memory loss.

Original languageEnglish
Pages (from-to)E7398-E7407
Number of pages10
JournalProceedings of the National Academy of Sciences of the United States of America
Volume115
Issue number31
Early online date25 Jun 2018
DOIs
Publication statusPublished - 31 Jul 2018

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Protein-Restricted Diet
Short-Term Memory
Mothers
Neurons
Brain
Proteins
Memory Disorders
Pregnancy
Neural Stem Cells
Lactation
Malnutrition
Cognition
Up-Regulation
Stem Cells
Cell Count
Parturition
Apoptosis
Genes

Cite this

Gould, Joanna M ; Smith, Phoebe J ; Airey, Chris J ; Mort, Emily J ; Airey, Lauren E ; Warricker, Frazer D M ; Pearson-Farr, Jennifer E ; Weston, Eleanor C ; Gould, Philippa J W ; Semmence, Oliver G ; Restall, Katie L ; Watts, Jennifer A ; McHugh, Patrick C ; Smith, Stephanie J ; Dewing, Jennifer M ; Fleming, Tom P ; Willaime-Morawek, Sandrine. / Mouse maternal protein restriction during preimplantation alone permanently alters brain neuron proportion and adult short-term memory. In: Proceedings of the National Academy of Sciences of the United States of America. 2018 ; Vol. 115, No. 31. pp. E7398-E7407.
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abstract = "Maternal protein malnutrition throughout pregnancy and lactation compromises brain development in late gestation and after birth, affecting structural, biochemical, and pathway dynamics with lasting consequences for motor and cognitive function. However, the importance of nutrition during the preimplantation period for brain development is unknown. We have previously shown that maternal low-protein diet (LPD) confined to the preimplantation period (Emb-LPD) in mice, with normal nutrition thereafter, is sufficient to induce cardiometabolic and locomotory behavioral abnormalities in adult offspring. Here, using a range of in vivo and in vitro techniques, we report that Emb-LPD and sustained LPD reduce neural stem cell (NSC) and progenitor cell numbers at E12.5, E14.5, and E17.5 through suppressed proliferation rates in both ganglionic eminences and cortex of the fetal brain. Moreover, Emb-LPD causes remaining NSCs to up-regulate the neuronal differentiation rate beyond control levels, whereas in LPD, apoptosis increases to possibly temper neuron formation. Furthermore, Emb-LPD adult offspring maintain the increase in neuron proportion in the cortex, display increased cortex thickness, and exhibit short-term memory deficit analyzed by the novel-object recognition assay. Last, we identify altered expression of fragile X family genes as a potential molecular mechanism for adverse programming of brain development. Collectively, these data demonstrate that poor maternal nutrition from conception is sufficient to cause abnormal brain development and adult memory loss.",
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Gould, JM, Smith, PJ, Airey, CJ, Mort, EJ, Airey, LE, Warricker, FDM, Pearson-Farr, JE, Weston, EC, Gould, PJW, Semmence, OG, Restall, KL, Watts, JA, McHugh, PC, Smith, SJ, Dewing, JM, Fleming, TP & Willaime-Morawek, S 2018, 'Mouse maternal protein restriction during preimplantation alone permanently alters brain neuron proportion and adult short-term memory', Proceedings of the National Academy of Sciences of the United States of America, vol. 115, no. 31, pp. E7398-E7407. https://doi.org/10.1073/pnas.1721876115

Mouse maternal protein restriction during preimplantation alone permanently alters brain neuron proportion and adult short-term memory. / Gould, Joanna M; Smith, Phoebe J; Airey, Chris J; Mort, Emily J; Airey, Lauren E; Warricker, Frazer D M; Pearson-Farr, Jennifer E; Weston, Eleanor C; Gould, Philippa J W; Semmence, Oliver G; Restall, Katie L; Watts, Jennifer A; McHugh, Patrick C; Smith, Stephanie J; Dewing, Jennifer M; Fleming, Tom P; Willaime-Morawek, Sandrine.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 115, No. 31, 31.07.2018, p. E7398-E7407.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Mouse maternal protein restriction during preimplantation alone permanently alters brain neuron proportion and adult short-term memory

AU - Gould, Joanna M

AU - Smith, Phoebe J

AU - Airey, Chris J

AU - Mort, Emily J

AU - Airey, Lauren E

AU - Warricker, Frazer D M

AU - Pearson-Farr, Jennifer E

AU - Weston, Eleanor C

AU - Gould, Philippa J W

AU - Semmence, Oliver G

AU - Restall, Katie L

AU - Watts, Jennifer A

AU - McHugh, Patrick C

AU - Smith, Stephanie J

AU - Dewing, Jennifer M

AU - Fleming, Tom P

AU - Willaime-Morawek, Sandrine

PY - 2018/7/31

Y1 - 2018/7/31

N2 - Maternal protein malnutrition throughout pregnancy and lactation compromises brain development in late gestation and after birth, affecting structural, biochemical, and pathway dynamics with lasting consequences for motor and cognitive function. However, the importance of nutrition during the preimplantation period for brain development is unknown. We have previously shown that maternal low-protein diet (LPD) confined to the preimplantation period (Emb-LPD) in mice, with normal nutrition thereafter, is sufficient to induce cardiometabolic and locomotory behavioral abnormalities in adult offspring. Here, using a range of in vivo and in vitro techniques, we report that Emb-LPD and sustained LPD reduce neural stem cell (NSC) and progenitor cell numbers at E12.5, E14.5, and E17.5 through suppressed proliferation rates in both ganglionic eminences and cortex of the fetal brain. Moreover, Emb-LPD causes remaining NSCs to up-regulate the neuronal differentiation rate beyond control levels, whereas in LPD, apoptosis increases to possibly temper neuron formation. Furthermore, Emb-LPD adult offspring maintain the increase in neuron proportion in the cortex, display increased cortex thickness, and exhibit short-term memory deficit analyzed by the novel-object recognition assay. Last, we identify altered expression of fragile X family genes as a potential molecular mechanism for adverse programming of brain development. Collectively, these data demonstrate that poor maternal nutrition from conception is sufficient to cause abnormal brain development and adult memory loss.

AB - Maternal protein malnutrition throughout pregnancy and lactation compromises brain development in late gestation and after birth, affecting structural, biochemical, and pathway dynamics with lasting consequences for motor and cognitive function. However, the importance of nutrition during the preimplantation period for brain development is unknown. We have previously shown that maternal low-protein diet (LPD) confined to the preimplantation period (Emb-LPD) in mice, with normal nutrition thereafter, is sufficient to induce cardiometabolic and locomotory behavioral abnormalities in adult offspring. Here, using a range of in vivo and in vitro techniques, we report that Emb-LPD and sustained LPD reduce neural stem cell (NSC) and progenitor cell numbers at E12.5, E14.5, and E17.5 through suppressed proliferation rates in both ganglionic eminences and cortex of the fetal brain. Moreover, Emb-LPD causes remaining NSCs to up-regulate the neuronal differentiation rate beyond control levels, whereas in LPD, apoptosis increases to possibly temper neuron formation. Furthermore, Emb-LPD adult offspring maintain the increase in neuron proportion in the cortex, display increased cortex thickness, and exhibit short-term memory deficit analyzed by the novel-object recognition assay. Last, we identify altered expression of fragile X family genes as a potential molecular mechanism for adverse programming of brain development. Collectively, these data demonstrate that poor maternal nutrition from conception is sufficient to cause abnormal brain development and adult memory loss.

KW - DOHaD

KW - Neural stem cells

KW - Neurogenesis

KW - Low-protein diet

KW - Maternal diet

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U2 - 10.1073/pnas.1721876115

DO - 10.1073/pnas.1721876115

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SP - E7398-E7407

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

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