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Brain development

Why do preterm brains lose specific interneurons?

Lacaille H, Vacher CM, Bakalar D, et al. · eNeuro · 2019

Open access · cc by · source: Europe PMC

Human preterm prefrontal cortex had fewer upper-layer SST and calbindin interneurons; a mouse combo of late maternal LPS plus postnatal hypoxia, but not either insult alone, reproduced that loss with later behavioral deficits.

Study at a glance

Design
Animal / in-vitro — Human preterm vs term BA9 immunohistochemistry plus a 2×2 mouse model of late LPS MIA and postnatal chronic sublethal hypoxia
N
N=27 · 13 term and 14 preterm human BA9 donors; GAD65-GFP mice, both sexes, four MIA×CSH groups from ≥2 litters each
Population
NIH NeuroBioBank term/preterm infant PFC plus C57BL/6 GAD65-GFP mouse offspring of both sexes
Outcome
PFC interneuron subtype density (SST, CLB, others), postnatal microglia, and later neurobehavior

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Key findings

Upper-layer SST and CLB interneurons were reduced in preterm human PFC. The same pattern appeared in mouse PFC only after MIA+CSH, linked to postnatal microglial activation during hypoxia only after MIA, plus long-term neurobehavioral deficits.

Methodology

Immunostained BA9 from 13 term and 14 preterm infants, then built a mouse model: 150 µg/kg LPS to dams at E15.5 and E16.5 plus 10.9% oxygen from P3–P10, with four MIA×CSH groups assessed anatomically and behaviorally.

Limitations

Postmortem infant samples and a mouse double-hit model cannot prove that targeting SST cells would prevent autism or schizophrenia after preterm birth.

How this study connects

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