Neurogenesis continues in the third trimester of pregnancy and is suppressed by premature birth

Sabrina Malik, Govindaiah Vinukonda, Linnea R. Vose, Daniel Diamond, Bala B R Bhimavarapu, Furong Hu, Muhammad T. Zia, Robert Hevner, Nada Zecevic, Praveen Ballabh

Research output: Contribution to journalArticle

80 Citations (Scopus)

Abstract

Premature infants exhibit neurodevelopmental delay and reduced growth of the cerebral cortex. However, the underlying mechanisms have remained elusive. Therefore, we hypothesized that neurogenesis in the ventricular and subventricular zones of the cerebral cortex would continue in the third trimester of pregnancy and that preterm birth would suppress neurogenesis. To test our hypotheses, we evaluated autopsy materials from human fetuses and preterm infants of 16 -35 gestational weeks (gw). We noted that both cycling and noncycling Sox2+ radial glial cells and Tbr2+ intermediate progenitors were abundant in human preterm infants until 28 gw. However, their densities consistently decreased from 16 through 28 gw. To determine the effect of premature birth on neurogenesis, we used a rabbit model and compared preterm [embryonic day 29 (E29), 3 d old] and term (E32,<2 hold) pups at an equivalent postconceptional age. Glutamatergic neurogenesis was suppressed in preterm rabbits, as indicated by the reduced number of Tbr2+intermediate progenitors and the increased number of Sox2+ radial glia. Additionally, hypoxia-inducible factor-1+, vascular endothelial growth factor, and erythropoietin were higher in term than preterm pups, reflecting the hypoxic intrauterine environment of just-born term pups. Proneural genes, including Pax6 and Neurogenin-1 and -2, were higher in preterm rabbit pups compared with term pups. Importantly, neurogenesis and associated factors were restored in preterm pups by treatment with dimethyloxallyl glycine, a hypoxia mimetic agent. Hence, glutamatergic neurogenesis continues in the premature infants, preterm birth suppresses neurogenesis, and hypoxia-mimetic agents might restore neurogenesis, enhance cortical growth, and improve neurodevelopmental outcome of premature infants.

Original languageEnglish (US)
Pages (from-to)411-423
Number of pages13
JournalJournal of Neuroscience
Volume33
Issue number2
DOIs
StatePublished - Jan 9 2013
Externally publishedYes

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Neurogenesis
Premature Birth
Third Pregnancy Trimester
Premature Infants
Rabbits
Cerebral Cortex
Ependymoglial Cells
Hypoxia-Inducible Factor 1
Lateral Ventricles
Growth
Erythropoietin
Neuroglia
Glycine
Vascular Endothelial Growth Factor A
Autopsy
Fetus
Genes

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Neurogenesis continues in the third trimester of pregnancy and is suppressed by premature birth. / Malik, Sabrina; Vinukonda, Govindaiah; Vose, Linnea R.; Diamond, Daniel; Bhimavarapu, Bala B R; Hu, Furong; Zia, Muhammad T.; Hevner, Robert; Zecevic, Nada; Ballabh, Praveen.

In: Journal of Neuroscience, Vol. 33, No. 2, 09.01.2013, p. 411-423.

Research output: Contribution to journalArticle

Malik, S, Vinukonda, G, Vose, LR, Diamond, D, Bhimavarapu, BBR, Hu, F, Zia, MT, Hevner, R, Zecevic, N & Ballabh, P 2013, 'Neurogenesis continues in the third trimester of pregnancy and is suppressed by premature birth', Journal of Neuroscience, vol. 33, no. 2, pp. 411-423. https://doi.org/10.1523/JNEUROSCI.4445-12.2013
Malik, Sabrina ; Vinukonda, Govindaiah ; Vose, Linnea R. ; Diamond, Daniel ; Bhimavarapu, Bala B R ; Hu, Furong ; Zia, Muhammad T. ; Hevner, Robert ; Zecevic, Nada ; Ballabh, Praveen. / Neurogenesis continues in the third trimester of pregnancy and is suppressed by premature birth. In: Journal of Neuroscience. 2013 ; Vol. 33, No. 2. pp. 411-423.
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AU - Hu, Furong

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