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Molecular Mechanisms of Early-Life Environmental Effects on Brain Development

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Neurobiology".

Deadline for manuscript submissions: 31 July 2026 | Viewed by 412

Special Issue Editor


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Guest Editor
Programs in Biology and Neuroscience, St. Mary’s College of Maryland, 18952 E Fisher Rd, St. Mary’s City, MD 20686, USA
Interests: developmental neurobiology; environmental toxicology; early-life influences on brain development

Special Issue Information

Dear Colleagues,

Early life represents a critical window during which environmental factors exert profound and lasting influences on brain development and function. This Special Issue, titled “Molecular Mechanisms of Early-Life Environmental Effects on Brain Development”, will showcase studies that explore the molecular and cellular pathways through which the early-life environment influences the development of the nervous system. We define “early-life environmental effects” broadly, encompassing prenatal and early postnatal exposures, including chemical and environmental toxicants, maternal health and physiology, patterns of maternal care, psychosocial and physiological stressors, physical activity, and nutrition.

We invite submissions that investigate the mechanisms underlying these influences, including, but not limited to, epigenetic regulation, gene–environment interactions, neuroimmune interactions, endocrine disruption, cellular stress and dysfunction, synaptic development, and circuit formation. Studies using in vitro systems, animal models, and human or translational approaches are all welcome. By integrating perspectives from molecular biology, neuroscience, developmental biology, toxicology, and epidemiology, this Special Issue will advance our understanding of how early-life environments influence neurodevelopment and long-term brain health. Topics of interest include, but are not limited to, the following:

  • Mechanisms linking prenatal or early postnatal environmental exposures to brain development;
  • Effects of environmental and chemical toxicants on neural developmental processes, including cell differentiation, synaptogenesis, and circuit formation;
  • Epigenetic regulation and gene-environment interactions in neurodevelopment;
  • Maternal health, metabolism, immune status, and stress as modulators of fetal and early postnatal brain development;
  • Neuroimmune and neuroendocrine pathways influenced by early-life environments;
  • Oxidative stress, mitochondrial dysfunction, and metabolic programming in the developing brain;
  • Molecular and cellular consequences of early-life stress, physical activity, nutrition, and maternal care;
  • Human and human-relevant models of early-life environmental influences on neurodevelopment;
  • Early-life environmental factors and risk or resilience for neurodevelopmental and neuropsychiatric disorders;

This Special Issue welcomes the following article types:

  • Original research articles presenting novel findings;
  • Review articles providing comprehensive and critical evaluations of the current literature;
  • Systematic reviews and meta-analyses, where appropriate;
  • Short communications reporting timely or emerging discoveries;
  • Perspectives or hypothesis articles proposing new mechanistic frameworks or conceptual models.

We look forward to receiving your contributions.

Dr. Sarah E. Latchney
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • early-life environment
  • brain development
  • neurodevelopmental programming
  • environmental exposures
  • developmental neurotoxicology
  • gene–environment interactions
  • maternal health
  • epigenetic regulation
  • neuroimmune interactions
  • endocrine disruption

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Published Papers (1 paper)

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Research

21 pages, 3681 KB  
Article
Fmr1 Deletion and Early-Life Stress Interact to Increase Cell Proliferation and Glial Populations at the Expense of Immature Neurons in the Adult Dentate Gyrus
by Sarah E. Latchney, Joan E. Ominuta, Lauryn E. L. Smitha, Katherine J. Blandin and Joaquin N. Lugo
Int. J. Mol. Sci. 2026, 27(10), 4356; https://doi.org/10.3390/ijms27104356 - 14 May 2026
Viewed by 161
Abstract
Fragile X Syndrome (FXS) is an inherited cause of intellectual disability and autism, arising from silencing of the Fmr1 gene and loss of Fragile X Messenger Ribonucleoprotein 1 (FMRP). FMRP is an RNA-binding protein critically involved in neurodevelopmental processes, including neurogenesis. We examined [...] Read more.
Fragile X Syndrome (FXS) is an inherited cause of intellectual disability and autism, arising from silencing of the Fmr1 gene and loss of Fragile X Messenger Ribonucleoprotein 1 (FMRP). FMRP is an RNA-binding protein critically involved in neurodevelopmental processes, including neurogenesis. We examined the proliferation and maturation of adult-born dentate granule cells (abDGCs) and glial populations in Fmr1 knockout (KO) and wild-type (WT) mice at 4, 12, and 24 weeks of age under control and early-life stress (ELS) conditions. Based on prior findings, we hypothesized that KO mice would exhibit increased neurogenesis and atypical responses to ELS compared with WT mice. Using immunohistochemistry, we quantified multiple stages of neurogenesis in the dentate gyrus, including proliferating (Ki67+), immature (doublecortin [DCX]+), and apoptotic (cleaved caspase-3 [CC3]+) cells. We also assessed glia using Iba1 (microglia) and GFAP (astrocytes) immunoreactivity. KO mice displayed significantly increased Ki67+ proliferating and reduced CC3+ apoptotic cells across ages, accompanied by increased Iba1+ and GFAP+ glial densities. However, KO mice exhibited fewer DCX+ neuroblasts at later time points. When reared in ELS conditions, KO mice show blunted or no changes in neurogenesis and glial populations relative to WT mice reared in ELS conditions or KO mice in control conditions. These results indicate that FMRP loss disrupts hippocampal neurogenesis by increasing cell proliferation while limiting neuronal maturation and expanding glial populations. Moreover, the absence of neurogenic and glial responses to ELS in KO mice highlights a gene–environment interaction that may influence FXS-related neuropathology by limiting the adaptive capacity of the hippocampal neurogenic niche. Full article
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