Regional distribution of nicotinic receptors during prenatal development of human brain and spinal cord
Abstract
The development of nicotinic acetylcholine receptors (nAChRs) in brains from human fetuses of 4-12 weeks gestational age was studied. The expression of nAChR subunit mRNAs was analyzed using reverse transcriptase-polymerase chain reaction. Expression of alpha 3, alpha 4, alpha 5, alpha 7, beta 2, beta 3 and beta 4 mRNA were all detected in the prenatal spinal cord, medulla oblongata, pons, cerebellum, mesencephalon, subcortical forebrain and cortex during first trimester development. Relative quantification of mRNA showed that the highest levels for alpha 3, alpha 4 and alpha 7 were expressed in the spinal cord, alpha 5 was most abundant in the cortex and beta 3 was highest in the cerebellum. beta 4 seemed to be equally distributed in all regions whereas beta 2 was high in the cortex and cerebellum. A comparison of expression of nAChR subunit mRNAs in the cortex and cerebellum of prenatal and aged (54-81 years) brain showed that mRNA levels for alpha 4, alpha 5, alpha 7, beta 2 and beta 4 were significantly higher in the prenatal cortex and cerebellum than in aged brain, whereas the level of alpha 3 transcript was similar, and beta 3 significantly higher in aged cortex. Specific binding of [3H]-epibatidine to prenatal brain membranes was detected as early as 4-5 weeks of gestation in the spinal cord, medulla oblongata, pons and subcortical forebrain. A positive correlation between gestational age and [3H]-epibatidine and [3H]-cytisine binding was found in several brain regions. The highest specific binding of [3H]-epibatidine and [3H]-cytisine was detected in the spinal cord, pons and medulla oblongata and the lowest in the cortex. Saturation analysis of [3H]-cytisine binding in both prenatal and aged brain were best fit by a model for a single site, whereas binding data for [3H]-epibatidine revealed two classes of binding sites. The early presence of nAChR proteins and gene transcripts shown in the present study suggests an important role for nAChRs in modulating dendritic outgrowth, establishment of neuronal connections and synaptogenesis during development.
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Even before the cholinergic projections arrive in the cortical areas, the nicotinic and muscarinic receptors are expressed on neural progenitors, playing a role in proliferation/differentiation and axonal guidance events.
“But even before the cholinergic projections arrive in the cortical areas, the nicotinic and muscarinic receptors are expressed on neural progenitors playing a role in proliferation/differentiation and axonal guidance events [214–217].”
From Development of prefrontal cortex (2022) · cites this paper as [214]
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References 59 · Cited by 159
- Authors
- Hellström-Lindahl, E., Gorbounova, O., Seiger, Å., Mousavi, M., & Nordberg, A.
- Affiliations
- Karolinska Institutet (SE)
- ORCID
- Nordberg, Agneta
- Venue
- Developmental Brain Research
- Publisher
- Elsevier BV
- Published
- 1998-06
- Volume
- 108
- Issue
- 1-2
- Pages
- 147-160
- ISSN
- 0165-3806 (ISSN-L)
- OpenAlex
- W1995897833
- Cited by
- 159
- References
- 59
- Citations by year
- 2025: 3 · 2024: 3 · 2023: 3 · 2022: 5 · 2021: 5 · 2020: 5 · 2019: 5 · 2018: 6 · 2017: 3 · 2016: 4 · 2015: 9 · 2014: 5 · 2013: 5 · 2012: 5
- FWCI
- 2.83
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Developmental Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Substance Exposure Effects
- Keywords
- nicotinic acetylcholine receptors, fetal brain development, human fetal brain, spinal cord development, epibatidine binding, synaptogenesis, dendritic outgrowth, gestational age
- MeSH terms
- Quinolizidine Alkaloids, Aged, Aged, 80 and over, Alkaloids, Azocines, Brain, Brain Chemistry, Cerebellum, Cerebral Cortex, Female, Fetus, Humans, Medulla Oblongata, Mesencephalon, Middle Aged, Nicotine, Pons, Pregnancy, Pregnancy Trimester, First, Protein Binding, Pyridines, Quinolizines, Radioligand Assay, Receptors, Nicotinic, RNA-Directed DNA Polymerase, RNA, Messenger, Spinal Cord, Tritium, DNA Probes, Polymerase Chain Reaction, Gene Expression Regulation, Developmental, Nicotinic Agonists, Bridged Bicyclo Compounds, Heterocyclic, Peptidylprolyl Isomerase
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