ArticlePediatric research2022
Adverse maternal environment affects hippocampal HTR2c variant expression and epigenetic characteristics in mouse offspring.
Article in Pediatric research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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Who cites it
4 citing papers in PubMed, 6 citations in OpenAlex.
- Maternal low-sodium diet impairs hippocampal neurogenesis and cognition in adult mouse offspring.American journal of physiology. Regulatory, integrative and comparative physiology · 2026Article
- Small Nucleolar RNAs and the Brain: Growing Evidence Supporting Their Role in Psychiatric Disorders.Biological psychiatry global open science · 2025Review
- Serotonergic receptor binding in the brainstem in the Sudden Infant Death Syndrome in a high-risk population.PloS one · 2025Article
- Adverse maternal environment alters Oprl1 variant expression in mouse hippocampus.Anatomical record (Hoboken, N.J. : 2007) · 2023Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAn adverse maternal environment (AME) predisposes progeny towards cognitive impairment in humans and mice. Cognitive impairment associates with hippocampal dysfunction. An important regulator of hippocampal function is the hippocampal serotonergic system. Dysregulation of hippocampal serotonin receptor 2c (HTR2c) expression is linked with cognitive impairment. HTR2c contains multiple mRNA variants and isoforms that are epigenetically regulated including DNA methylation, histone modifications, and small nucleolar RNA MBII-52. We tested the hypotheses that AME increases HTR2c variant expression and alters epigenetic modifications along the HTR2c gene locus.
methodsWe create an AME through maternal Western diet and prenatal environmental stress in the mouse. We analyzed hippocampal HTR2c and variants' expression, DNA methylation and histone modifications along the gene locus, and MBII-52 levels in postnatal day 21 offspring.
resultsAME significantly increased the expressions of total HTR2c and full-length variants (V201 and V202) concurrently with an altered epigenetic profile along the HTR2c gene locus in male offspring hippocampi. Moreover, increased full-length variants' expression in AME males was in line with increased MBII-52 levels.
conclusionsAME affects male offspring hippocampal expression of HTR2c and full-length variants via epigenetic mechanisms. Altered hippocampal HTR2c expression may contribute to cognitive impairment seen in adult males in this model. IMPACT: The key message of our article is that an adverse maternal environment increases expression of total HTR2c mRNA and protein, alters proportions of HTR2c mRNA variants, and impacts HTR2c epigenetic modifications in male offspring hippocampi relative to controls. Our findings add to the literature by providing the first report of altered HTR2c mRNA variant expression in association with altered epigenetic modifications in the hippocampus of offspring mice exposed to an adverse maternal environment. Our findings suggest that an adverse maternal environment affects the expression of genes previously determined to regulate cognitive function through an epigenetic mechanism in a sex-specific manner.
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