Neonatal Maternal Separation Impairs Prefrontal Cortical Myelination and Cognitive Functions in Rats Through Activation of Wnt Signaling
Abstract
Adverse early-life experience such as depriving the relationship between parents and children induces permanent phenotypic changes, and impairs the cognitive functions associated with the prefrontal cortex (PFC). However, the underlying mechanism remains unclear. In this work, we used rat neonatal maternal separation (NMS) model to illuminate whether and how NMS in early life affects cognitive functions, and what the underlying cellular and molecular mechanism is. We showed that rat pups separated from their dam 3 h daily during the first 3 postnatal weeks alters medial prefrontal cortex (mPFC) myelination and impairs mPFC-dependent behaviors. Myelination appears necessary for mPFC-dependent behaviors, as blockade of oligodendrocytes (OLs) differentiation or lysolecithin-induced demyelination, impairs mPFC functions. We further demonstrate that histone deacetylases 1/2 (HDAC1/2) are drastically reduced in NMS rats. Inhibition of HDAC1/2 promotes Wnt activation, which negatively regulates OLs development. Conversely, selective inhibition of Wnt signaling by XAV939 partly rescue myelination arrestment and behavior deficiency caused by NMS. These findings indicate that NMS impairs mPFC cognitive functions, at least in part, through modulation of oligodendrogenesis and myelination. Understanding the mechanism of NMS on mPFC-dependent behaviors is critical for developing pharmacological and psychological interventions for child neglect and abuse.
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- Authors
- Yang, Y., Cheng, Z., Tang, H., Jiao, H., Sun, X., Cui, Q., Luo, F., Pan, H., Ma, C., & Li, B.
- Affiliations
- Nanchang University (CN)
- Venue
- Cerebral Cortex
- Publisher
- Oxford University Press (OUP)
- Published
- 2016-05-13
- Volume
- 27
- Issue
- 5
- Pages
- bhw121
- ISSN
- 1047-3211 (ISSN-L)
- 1460-2199
- OpenAlex
- W2374240255
- Cited by
- 124
- References
- 13
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 11 · 2023: 17 · 2022: 12 · 2021: 20 · 2020: 12 · 2019: 16 · 2018: 12 · 2017: 8 · 2016: 4
- FWCI
- 6.81
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cerebral Cortex (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81471116)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- neonatal maternal separation, Wnt signaling, oligodendrocyte differentiation, oligodendrogenesis, demyelination, XAV939, childhood adversity, child neglect and abuse, cognitive impairment
- MeSH terms
- Animals, Animals, Newborn, Anxiety, Cognition Disorders, Demyelinating Diseases, Myelin Basic Protein, Enzyme Inhibitors, Exploratory Behavior, Heterocyclic Compounds, 3-Ring, Histone Deacetylases, Lipopolysaccharides, Maternal Deprivation, Valproic Acid, Rats, Sprague-Dawley, Prefrontal Cortex, Gene Expression Regulation, Developmental, Maze Learning, Wnt Proteins, Rats, Neurogenesis, Wnt Signaling Pathway
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