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Title: The Role of Redox Dysregulation in the Effects of Prenatal Stress on Embryonic Interneuron Migration.

Authors: Bittle, Jada; Menezes, Edenia C; McCormick, Michael L; Spitz, Douglas R; Dailey, Michael; Stevens, Hanna E

Published In Cereb Cortex, (2019 12 17)

Abstract: Maternal stress during pregnancy is associated with increased risk of psychiatric disorders in offspring, but embryonic brain mechanisms disrupted by prenatal stress are not fully understood. Our lab has shown that prenatal stress delays inhibitory neural progenitor migration. Here, we investigated redox dysregulation as a mechanism for embryonic cortical interneuron migration delay, utilizing direct manipulation of pro- and antioxidants and a mouse model of maternal repetitive restraint stress starting on embryonic day 12. Time-lapse, live-imaging of migrating GAD67GFP+ interneurons showed that normal tangential migration of inhibitory progenitor cells was disrupted by the pro-oxidant, hydrogen peroxide. Interneuron migration was also delayed by in utero intracerebroventricular rotenone. Prenatal stress altered glutathione levels and induced changes in activity of antioxidant enzymes and expression of redox-related genes in the embryonic forebrain. Assessment of dihydroethidium (DHE) fluorescence after prenatal stress in ganglionic eminence (GE), the source of migrating interneurons, showed increased levels of DHE oxidation. Maternal antioxidants (N-acetylcysteine and astaxanthin) normalized DHE oxidation levels in GE and ameliorated the migration delay caused by prenatal stress. Through convergent redox manipula-tions, delayed interneuron migration after prenatal stress was found to critically involve redox dysregulation. Redox biology during prenatal periods may be a target for protecting brain development.

PubMed ID: 30877797 Exiting the NIEHS site

MeSH Terms: Animals; Antioxidants/pharmacology; Brain/drug effects; Brain/embryology*; Brain/metabolism; Cell Movement/drug effects; Cell Movement/physiology; Disease Models, Animal; Female; Interneurons/drug effects; Interneurons/metabolism*; Mice; Neurogenesis/physiology*; Oxidation-Reduction; Oxidative Stress/drug effects; Oxidative Stress/physiology; Pregnancy; Prenatal Exposure Delayed Effects/metabolism*; Restraint, Physical/adverse effects; Stress, Psychological/complications*; Stress, Psychological/metabolism

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