ArticleNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology2015
Functional Uncoupling NMDAR NR2A Subunit from PSD-95 in the Prefrontal Cortex: Effects on Behavioral Dysfunction and Parvalbumin Loss after Early-Life Stress.
Article in Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 22 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 2 syntheses or guidelines pooled it, 60 citations in OpenAlex.
- Prefrontal and Hippocampal Parvalbumin Interneurons in Animal Models for Schizophrenia: A Systematic Review and Meta-analysis.Schizophrenia bulletin · 2024Pooled it
- Pooled it
- Parvalbumin interneurons under stress: converging mechanisms of vulnerability.The international journal of neuropsychopharmacology · 2026Review
- Prefrontal parvalbumin interneurons mediate CRHR1-dependent early-life stress-induced cognitive deficits in adolescent male mice.Molecular psychiatry · 2025Article
- Article
- CB1R blockade unmasks TRPV1-mediated contextual fear generalization in female, but not male rats.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2023Article
- Oestrogen treatment restores dentate gyrus development in premature newborns by IGF1 regulation.Journal of cellular and molecular medicine · 2023Article
- The causal involvement of the BDNF-TrkB pathway in dentate gyrus in early-life stress-induced cognitive deficits in male mice.Translational psychiatry · 2023Article
- Circuit- and laminar-specific regulation of medial prefrontal neurons by chronic stress.Cell & bioscience · 2023Article
- Elevated insulin growth factor-1 in dentate gyrus induces cognitive deficits in pre-term newborns.Cerebral cortex (New York, N.Y. : 1991) · 2023Article
- Involvement of brain cell phenotypes in stress-vulnerability and resilience.Frontiers in neuroscience · 2023Review
- Maternal separation modifies spontaneous synaptic activity in the infralimbic cortex of stress-resilient male rats.PloS one · 2023Article
- Parvalbumin interneuron alterations in stress-related mood disorders: A systematic review.Neurobiology of stress · 2021Review
- Sex Differences in Affective Dysfunction and Alterations in Parvalbumin in Rodent Models of Early Life Adversity.Frontiers in behavioral neuroscience · 2021Review
- Trajectories of Mother-Infant Communication: An Experiential Measure of the Impacts of Early Life Adversity.Frontiers in human neuroscience · 2021Article
- Article
- Early-Life Stress Alters Synaptic Plasticity and mTOR Signaling: Correlation With Anxiety-Like and Cognition-Related Behavior.Frontiers in genetics · 2020Article
- Acute and Chronic Sleep Deprivation-Related Changes in N-methyl-D-aspartate Receptor-Nitric Oxide Signalling in the Rat Cerebral Cortex with Reference to Aging and Brain Lateralization.International journal of molecular sciences · 2019Article
- Cross-Generational Transmission of Early Life Stress Effects on HPA Regulators and Bdnf Are Mediated by Sex, Lineage, and Upbringing.Frontiers in behavioral neuroscience · 2019Article
- Adolescence as a neurobiological critical period for the development of higher-order cognition.Neuroscience and biobehavioral reviews · 2018Review
Corrections and comments
- Erratum issued
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Exposure to early-life stress increases vulnerability to psychiatric disorders, including depression, schizophrenia, and anxiety. Growing evidence implicates aberrant development of the prefrontal cortex (PFC) in the effects of early-life stress, which often emerge in adolescence or young adulthood. Specifically, early-life stress in the form of maternal separation (MS) in rodents has been shown to decrease parvalbumin (PVB)-positive interneurons in the adolescent PFC; however, the mechanism underpinning behavioral dysfunction and PVB loss is not yet known. We recently reported that MS causes overexpression of the NMDA subunit NR2A in the PFC of adolescent rats. Elevated PFC NR2A is also found in developmental models of schizophrenia and is correlated with behavioral deficits, acting largely through its association with the postsynaptic protein PSD-95. In addition, adolescent maturation of PVB-positive interneurons relies on NR2A-driven NMDA activity. Therefore, it is possible that the NR2A/PSD-95 signaling complex has a role in adolescent MS effects. Here, we aimed to determine whether a discrete manipulation of PFC NR2A could prevent MS effects on PFC-controlled behaviors, including cognition, anxiety, and novelty-induced hyperlocomotion, as well as PVB loss in adolescence. We intracranially infused the NR2A-specific blocking peptide TAT2A in order to uncouple NR2A from PSD-95 in the early-adolescent PFC, without antagonizing the NMDA receptor. We demonstrated that MS rats treated with TAT2A during early adolescence were protected from MS-induced PVB loss and exhibited less anxious behavior than those infused with control peptide. These data implicate NR2A-related N-methyl-D-aspartate receptor development in adolescent behavioral and neural consequences of early-life stress.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.