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

Yang, Guang; Cancino, Gonzalo I; Zahr, Siraj K.; Guskjolen, Axel; Voronova, Anastassia; Gallagher, Denis; Frankland, Paul W.; Kaplan, David R.; Miller, Freda D.

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 neuro-genesis 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.

Más información

Título según WOS: ID WOS:000385853600010 Not found in local WOS DB
Título de la Revista: CELL REPORTS
Volumen: 17
Número: 4
Editorial: Cell Press
Fecha de publicación: 2016
Página de inicio: 1022
Página final: 1036
DOI:

10.1016/j.celrep.2016.09.067

Notas: ISI