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Published on: November 20, 2015
Association of impaired neuronal migration with cognitive deficits in extremely preterm infants
Ken-Ichiro Kubo1, Kimiko Deguchi1,2,3, Taku Nagai4
1Department of Anatomy, Keio University School of Medicine, Tokyo, Japan.
Insights
Brain injury in extremely preterm infants can disrupt neuronal migration, potentially leading to cognitive impairments. This study in mice suggests that addressing brain activity may improve cognitive deficits in preterm infants.
Area of Science:
- Neuroscience
- Developmental Biology
- Neonatal Medicine
Background:
- Extremely preterm infants (born before 28 gestational weeks) often experience cognitive impairment.
- The precise mechanisms linking preterm birth complications to cognitive deficits remain unclear.
- Neuronal migration, crucial for brain development, continues past the earliest viable gestational age.
Purpose of the Study:
- To investigate if preterm brain injury impacts neuronal migration.
- To explore the link between altered neuronal migration and cognitive deficits.
- To identify potential therapeutic targets for cognitive impairment in preterm infants.
Main Methods:
- Examined human neocortical development and neuronal migration.
- Induced brain injury in mouse embryos via maternal uterine artery occlusion.
- Assessed neuronal migration, axonal wiring, and cognitive function in mice.
- Investigated the effect of medial prefrontal cortex activation on cognitive deficits.
Main Results:
- Preterm brain injury in mice caused delayed neuronal migration and ectopic neurons.
- Mice exhibited abnormal neuronal alignment and corticocortical wiring.
- Surviving mice showed cognitive deficits, particularly in working memory.
- Activation of affected brain regions improved working memory, suggesting reduced neuronal activity.
Conclusions:
- Preterm brain injury can disrupt critical neuronal migration processes.
- Altered neuronal migration is a potential contributor to cognitive impairment in extremely preterm infants.
- Targeting neuronal activity in specific brain regions may ameliorate cognitive deficits.
Abstract:
Many extremely preterm infants (born before 28 gestational weeks [GWs]) develop cognitive impairment in later life, although the underlying pathogenesis is not yet completely understood. Our examinations of the developing human neocortex confirmed that neuronal migration continues beyond 23 GWs, the gestational week at which extremely preterm infants have live births. We observed larger numbers of ectopic neurons in the white matter of the neocortex in human extremely preterm infants with brain injury and hypothesized that altered neuronal migration may be associated with cognitive impairment in later life. To confirm whether preterm brain injury affects neuronal migration, we produced brain damage in mouse embryos by occluding the maternal uterine arteries. The mice showed delayed neuronal migration, ectopic neurons in the white matter, altered neuronal alignment, and abnormal corticocortical axonal wiring. Similar to human extremely preterm infants with brain injury, the surviving mice exhibited cognitive deficits. Activation of the affected medial prefrontal cortices of the surviving mice improved working memory deficits, indicating that decreased neuronal activity caused the cognitive deficits. These findings suggest that altered neuronal migration altered by brain injury might contribute to the subsequent development of cognitive impairment in extremely preterm infants.
