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Preterm birth alters the maturation of the GABAergic system in the human prefrontal cortex

Helene Lacaille, Claire-Marie Vacher, Anna A. Penn
doi: https://doi.org/10.1101/2021.12.14.472624
Helene Lacaille
1Department of Pediatrics, Columbia University, New York-Presbyterian Morgan Stanley Children’s Hospital, New York, NY, USA
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Claire-Marie Vacher
1Department of Pediatrics, Columbia University, New York-Presbyterian Morgan Stanley Children’s Hospital, New York, NY, USA
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Anna A. Penn
1Department of Pediatrics, Columbia University, New York-Presbyterian Morgan Stanley Children’s Hospital, New York, NY, USA
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  • For correspondence: aap2216@columbia.edu
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Abstract

Developmental changes in GABAergic and glutamatergic systems during frontal lobe development have been hypothesized to play a key role in neurodevelopmental disorders seen in children born very preterm or low birth weight, but the associated cellular changes have not yet been identified. Here we studied the molecular development of the GABAergic system specifically in the dorsolateral prefrontal cortex, a region that that has been implicated in neurodevelopmental and psychiatric disorders. The maturation state of the GABAergic system in this region was assessed in human post-mortem brain samples, from term infants ranging in age from 0 to 8 months (n=17 male, 9 female). Gene expression was measured for 47 GABAergic genes and used to calculate a maturation index. This maturation index was significantly more dynamic in male than female infants. To evaluate the impact of premature birth on the GABAergic system development, samples from one-month-old term (n=9 male, 4 female) and one-month corrected-age (n=8 male, 6 female) very preterm infants, were compared using the same gene list and methodology. The maturation index for the GABAergic system was significantly lower (–50% p<0.05) in male preterm infants, with major alterations in genes linked to GABAergic function in astrocytes, suggesting astrocytic GABAergic developmental changes as a new cellular mechanism underlying preterm brain injury.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted December 15, 2021.
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Preterm birth alters the maturation of the GABAergic system in the human prefrontal cortex
Helene Lacaille, Claire-Marie Vacher, Anna A. Penn
bioRxiv 2021.12.14.472624; doi: https://doi.org/10.1101/2021.12.14.472624
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Preterm birth alters the maturation of the GABAergic system in the human prefrontal cortex
Helene Lacaille, Claire-Marie Vacher, Anna A. Penn
bioRxiv 2021.12.14.472624; doi: https://doi.org/10.1101/2021.12.14.472624

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