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A Glo1-Methylglyoxal Pathway that Is Perturbed in Maternal Diabetes Regulates Embryonic and Adult Neural Stem Cell Pools in Murine Offspring.

Abstract：

:Maternal diabetes is known to adversely influence brain development in offspring. Here, we provide evidence that this involves the circulating metabolite methylglyoxal, which is increased in diabetes, and its detoxifying enzyme, glyoxalase 1 (Glo1), which when mutated is associated with neurodevelopmental disorders. Specifically, when Glo1 levels were decreased in embryonic mouse cortical neural precursor cells (NPCs), this led to premature neurogenesis and NPC depletion embryonically and long-term alterations in cortical neurons postnatally. Increased circulating maternal methylglyoxal caused similar changes in embryonic cortical precursors and neurons and long-lasting changes in cortical neurons and NPCs in adult offspring. Depletion of embryonic and adult NPCs was also observed in murine offspring exposed to a maternal diabetic environment. Thus, the Glo1-methylglyoxal pathway integrates maternal and NPC metabolism to regulate neural development, and perturbations in this pathway lead to long-lasting alterations in adult neurons and NPC pools.

journal_name

Cell Rep

journal_title

Cell reports

authors

Yang G,Cancino GI,Zahr SK,Guskjolen A,Voronova A,Gallagher D,Frankland PW,Kaplan DR,Miller FD

doi

10.1016/j.celrep.2016.09.067

subject

Has Abstract

pub_date

2016-10-18 00:00:00

pages

1022-1036

issue

4

issn

2211-1247

pii

S2211-1247(16)31323-7

journal_volume

17

pub_type

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