Stress during a critical postnatal period induces region-specific structural abnormalities and dysfunction of the prefrontal cortex via CRF1
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During the early postnatal period, environmental influences play a pivotal role in shaping the development of the neocortex, including the prefrontal cortex (PFC) that is crucial for working memory and goal-directed actions. Exposure to stressful experiences during this critical period may disrupt the development of PFC pyramidal neurons and impair the wiring and function of related neural circuits. However, the molecular mechanisms of the impact of early-life stress on PFC development and function are not well understood. In this study, we found that repeated stress exposure during the first postnatal week hampered dendritic development in layers II/III and V pyramidal neurons in the dorsal agranular cingulate cortex (ACd) and prelimbic cortex (PL) of neonatal mice. The deleterious effects of early postnatal stress on structural plasticity persisted to adulthood only in ACd layer V pyramidal neurons. Most importantly, concurrent blockade of corticotropin-releasing factor receptor 1 (CRF1) by systemic antalarmin administration (20 μg/g of body weight) during early-life stress exposure prevented stress-induced apical dendritic retraction and spine loss in ACd layer V neurons and impairments in PFC-dependent cognitive tasks. Moreover, the magnitude of dendritic regression, especially the shrinkage of apical branches, of ACd layer V neurons predicted the degree of cognitive deficits in stressed mice. Our data highlight the region-specific effects of early postnatal stress on the structural plasticity of prefrontal pyramidal neurons, and suggest a critical role of CRF1 in modulating early-life stress-induced prefrontal abnormalities.
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These structural changes are accompanied by changes to cognition supported by frontal circuits.
“These structural changes are accompanied by changes to cognition supported by frontal circuits (Lovic and Fleming, 2004; Thomas et al., 2015; Yang et al., 2015).”
From Does puberty mark a transition in sensitive periods for plasticity in the associative neocortex? (2017) · cites this paper as Yang et al., 2015
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- Authors
- Yang, X.-D., Liao, X.-M., Uribe-Mariño, A., Liu, R., Xie, X.-M., Jia, J., Su, Y.-A., Li, J.-T., Schmidt, M. V., Wang, X.-D., & Si, T.-M.
- Affiliations
- Peking University (CN)
- Max Planck Institute of Psychiatry (DE)
- Shanxi Medical University (CN)
- Venue
- Neuropsychopharmacology
- Published
- 2014-11-18
- Volume
- 40
- Issue
- 5
- Pages
- 1203-1215
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC4367464
- OpenAlex
- W1972646149
- Cited by
- 93
- References
- 56
- Citations by year
- 2026: 6 · 2025: 2 · 2024: 8 · 2023: 10 · 2022: 9 · 2021: 8 · 2020: 11 · 2019: 11 · 2018: 6 · 2017: 11 · 2016: 8 · 2015: 3
- FWCI
- 3.60
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- International Brain Research Organization
- National Natural Science Foundation of China (81301152, 81171284)
- Specialized Research Fund for the Doctoral Program of Higher Education of China (20120001110046)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Keywords
- early life stress, postpartum period, prefrontal cortex, corticotropin-releasing hormone receptor 1, antalarmin, dendritic development, spine loss, pyramidal neurons, prelimbic cortex, structural plasticity, cognitive impairment
- MeSH terms
- CRF Receptor, Type 1, Animals, Animals, Newborn, Anxiety Disorders, Cognition Disorders, Disease Models, Animal, Female, Hormone Antagonists, Male, Mice, Inbred C57BL, Pyrimidines, Pyrroles, Random Allocation, Stress, Psychological, Prefrontal Cortex, Pyramidal Cells, Receptors, Corticotropin-Releasing Hormone, Dendritic Spines
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