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

Mouse maternal protein restriction during preimplantation alone permanently alters brain neuron proportion and adult short-term memory
Mouse maternal protein restriction during preimplantation alone permanently alters brain neuron proportion and adult short-term memory
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 maternal low protein diet 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, we report, using a range of in vivo and in vitro techniques, that Emb-LPD and sustained LPD reduce neural stem cell (NSCs) 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 upregulate 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 short-term memory deficit analyzed by the novel object recognition assay. Lastly, we identify altered expression of fragile X family genes as a potential molecular mechanism for adverse programming of brain development. Collectively, these data demonstrate poor maternal nutrition from conception is sufficient to cause abnormal brain development and adult memory loss.
E7398-E7407
Gould, Joanna, Mary
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Smith, Phoebe J.
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Airey, Chris J.
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Mort, Emily J.
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Airey, Lauren E
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Warricker, Frazer DM
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Pearson-Farr, Jennifer, Elizabeth
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Weston, Eleanor C
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Gould, Philippa JW
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Semmence, Oliver G
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Restall, Katie L.
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Watts, J.A
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McHugh, Patrick C
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Smith, Stephanie J
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Dewing, Jennifer M.
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Fleming, Thomas P.
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Willaime-Morawek, Sandrine
24a2981f-aa9e-4bf6-ad12-2ccf6b49f1c0
Gould, Joanna, Mary
96c504c1-273b-4104-98e6-87931fe763bf
Smith, Phoebe J.
0514b7c4-d671-4b68-8a95-9b5afddab988
Airey, Chris J.
92a7831b-b617-42e0-8ebd-bd794ecfd21c
Mort, Emily J.
8b3acc11-a8ea-418e-b4d8-47d4ec29118f
Airey, Lauren E
57265993-8217-4bad-9f92-92d2de0aa317
Warricker, Frazer DM
57296e2b-40de-43ce-bf95-007af1bae9e7
Pearson-Farr, Jennifer, Elizabeth
e7da2e7c-e8e8-47d6-aca4-86b1a5b90653
Weston, Eleanor C
dad095ec-0eeb-4938-b787-b359c0d57a93
Gould, Philippa JW
6850b051-665a-40f6-a4ee-30399a0246d0
Semmence, Oliver G
1dd566b4-3651-40d1-98e6-27a09cb1245a
Restall, Katie L.
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Watts, J.A
b06819fc-61a2-4b7c-8d51-9f0829b1212d
McHugh, Patrick C
8495a0a9-d249-4f30-9464-16ff570b0656
Smith, Stephanie J
ee107f53-c871-4a11-b494-dd185cdf5f1e
Dewing, Jennifer M.
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Fleming, Thomas P.
2abf761a-e5a1-4fa7-a2c8-12e32d5d4c03
Willaime-Morawek, Sandrine
24a2981f-aa9e-4bf6-ad12-2ccf6b49f1c0

Gould, Joanna, Mary, Smith, Phoebe J., Airey, Chris J., Mort, Emily J., Airey, Lauren E, Warricker, Frazer DM, Pearson-Farr, Jennifer, Elizabeth, Weston, Eleanor C, Gould, Philippa JW, Semmence, Oliver G, Restall, Katie L., Watts, J.A, McHugh, Patrick C, Smith, Stephanie J, Dewing, Jennifer M., Fleming, Thomas P. and Willaime-Morawek, Sandrine (2018) Mouse maternal protein restriction during preimplantation alone permanently alters brain neuron proportion and adult short-term memory. Proceedings of National Academy of Sciences of the United States of America, 115 (13), E7398-E7407. (doi:10.1073/pnas.1721876115).

Record type: Article

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 maternal low protein diet 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, we report, using a range of in vivo and in vitro techniques, that Emb-LPD and sustained LPD reduce neural stem cell (NSCs) 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 upregulate 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 short-term memory deficit analyzed by the novel object recognition assay. Lastly, we identify altered expression of fragile X family genes as a potential molecular mechanism for adverse programming of brain development. Collectively, these data demonstrate poor maternal nutrition from conception is sufficient to cause abnormal brain development and adult memory loss.

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Accepted/In Press date: 30 May 2018
e-pub ahead of print date: 25 June 2018
Published date: 31 July 2018

Identifiers

Local EPrints ID: 421704
URI: http://eprints.soton.ac.uk/id/eprint/421704
PURE UUID: 2a9a29cb-a0e8-4718-9221-62cdef5e0751
ORCID for Sandrine Willaime-Morawek: ORCID iD orcid.org/0000-0002-1121-6419

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Date deposited: 21 Jun 2018 16:30
Last modified: 26 Nov 2021 06:26

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Contributors

Author: Joanna, Mary Gould
Author: Phoebe J. Smith
Author: Chris J. Airey
Author: Emily J. Mort
Author: Lauren E Airey
Author: Frazer DM Warricker
Author: Jennifer, Elizabeth Pearson-Farr
Author: Eleanor C Weston
Author: Philippa JW Gould
Author: Oliver G Semmence
Author: Katie L. Restall
Author: J.A Watts
Author: Patrick C McHugh
Author: Stephanie J Smith
Author: Jennifer M. Dewing

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