Effects of Ethanol Exposure In Utero on Cajal–Retzius Cells in the Developing Cortex
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Background: Prenatal exposure to ethanol exerts teratogenic effects on the developing brain. Here, we tested the hypothesis that exposure to ethanol in utero alters the disposition of Cajal–Retzius cells that play a key role in orchestrating proliferation, migration, and laminar integration of cortical neurons in the embryonic cortex. Methods: Pregnant Ebf2‐EGFP mice, harboring EGFP‐fluorescent Cajal–Retzius cells, were subjected to a 2% w/w ethanol consumption regimen starting at neural tube closure and lasting throughout gestation. Genesis of Cajal–Retzius cells was assessed by means of 5‐bromo‐2‐deoxyuridine (BrdU) immunofluorescence at embryonic day 12.5, their counts and distribution were determined between postnatal day (P)0 and P4, patch clamp electrophysiology was performed between P2 and P3 to analyze GABA‐mediated synaptic activity, and open‐field behavioral testing was conducted in P45‐P50 adolescents. Results: In Ebf2‐EGFP embryos exposed to ethanol in utero, we found increased BrdU labeling and expanded distribution of Cajal–Retzius cells in the cortical hem, pointing to increased genesis and proliferation. Postnatally, we found an increase in Cajal–Retzius cell number in cortical layer I. In addition, they displayed altered patterning of spontaneous GABA‐mediated synaptic barrages and enhanced GABA‐mediated synaptic activity, suggesting enhanced GABAergic tone. Conclusions: These findings, together, underscore that Cajal–Retzius cells contribute to the ethanol‐induced aberration of cortical development and abnormal GABAergic neurotransmission at the impactful time when intracortical circuits form.
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Structurally, the prefrontal cortical thickness is affected after prenatal alcohol exposure and it matures with a smaller number of excitatory neurons and more GABAergic ones, disrupting the excitatory/inhibitory balance severely.
“Structurally, the prefrontal cortical thickness is affected after prenatal alcohol exposure and it matures with a smaller number of excitatory neurons and more GABAergic ones disrupting the excitatory/inhibitory balance severely [319–321].”
From Development of prefrontal cortex (2022) · cites this paper as [320]
The Results report increased Cajal–Retzius cell density in the neonatal prefrontal cortex after prenatal ethanol exposure, and the Discussion reports increased GABAergic tone and a possible disturbance of inhibitory/excitatory balance (page numbers unavailable). The paper does not establish altered prefrontal cortical thickness, fewer excitatory neurons, or more GABAergic neurons; increased GABAergic input is not a count of GABAergic cells. (LLM, conf=0.87)
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- Authors
- Skorput, A. G. J., & Yeh, H. H.
- Affiliations
- Dartmouth–Hitchcock Medical Center (US)
- Corresponding author
- Yeh, Hermes H.
- ORCID
- Yeh, Hermes H.
- Venue
- Alcoholism: Clinical and Experimental Research
- Publisher
- Wiley
- Published
- 2015-04-06
- Volume
- 39
- Issue
- 5
- Pages
- 853-862
- ISSN
- 0145-6008 (ISSN-L)
- 1530-0277
- PMC
- PMC4744082
- OpenAlex
- W2153395189
- Cited by
- 12
- References
- 49
- Citations by year
- 2026: 1 · 2023: 1 · 2021: 2 · 2020: 4 · 2018: 1 · 2017: 1 · 2016: 1 · 2015: 1
- FWCI
- 1.33
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Alcoholism Clinical and Experimental Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (R01 AA023410-01)
- Topics
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Fetal and Pediatric Neurological Disorders
- Keywords
- prenatal alcohol exposure, Cajal-Retzius cells, fetal alcohol spectrum disorders, cortical development, GABAergic neurotransmission, neuronal proliferation, cortical lamination, spontaneous synaptic activity, teratogenicity
- MeSH terms
- Reelin Protein, Ethanol, Animals, Cerebral Cortex, Female, Mice, Transgenic, Motor Activity, Neurons, Pregnancy, Prenatal Exposure Delayed Effects, Cell Proliferation, Mice, Miniature Postsynaptic Potentials, Neurogenesis, GABAergic Neurons
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