Prenatal carbon monoxide impairs migration of interneurons into the cerebral cortex

被引：5

作者：

Trentini, John F. ^{[1
]}

O'Neill, J. Timothy ^{[1
,2
]}

Poluch, Sylvie ^{[1
,3
]}

Juliano, Sharon L. ^{[1
,3
]}

机构：

[1] Uniformed Serv Univ Hlth Sci, Grad Program Neurosci, Bethesda, MD 20814 USA

[2] Uniformed Serv Univ Hlth Sci, Dept Pediat, Bethesda, MD 20814 USA

[3] Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA

来源：

NEUROTOXICOLOGY | 2016年 / 53卷

关键词：

Carbon monoxide; Neocortical development; Neuronal migration; BrdU; Interneuron; SOLUBLE GUANYLYL CYCLASE; TOBACCO-SMOKE EXPOSURE; NITRIC-OXIDE; NEURONAL MIGRATION; MATERNAL SMOKING; VISUAL-CORTEX; GANGLIONIC EMINENCE; PREPULSE INHIBITION; CYCLIC-NUCLEOTIDES; STARTLE RESPONSE;

D O I：

10.1016/j.neuro.2015.11.002

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Prenatal exposure to carbon monoxide (CO) disrupts brain development, however little is known about effects on neocortical maturation. We exposed pregnant mice to CO from embryonic day 7 (E7) until birth. To study the effect of CO on neuronal migration into the neocortex we injected BrdU during corticogenesis and observed misplaced BrdU+ cells. The majority of cells not in their proper layer colocalized with GAD65/67, suggesting impairment of interneuron migration; interneuron subtypes were also affected. We subsequently followed interneuron migration from EIS organotypic cultures of mouse neocortex exposed to CO; the leading process length of migrating neurons diminished. To examine an underlying mechanism, we assessed the effects of CO on the cellular cascade mediating the cytoskeletal protein vasodilator-stimulated phosphoprotein (VASP). CO exposure resulted in decreased cGMP and in a downstream target, phosphorylated VASP. Organotypic cultures grown in the presence of the phosphodiesterase inhibitor IBMX resulted in a recovery of the leading processes. These data support the idea that CO acts as a signaling molecule and impairs function and neuronal migration by acting through the CO/NO-cGMP pathway. In addition, treated mice demonstrated functional impairment in behavioral tests. Published by Elsevier Inc.

引用

页码：31 / 44

页数：14