Aberrant maturation and connectivity of prefrontal cortex in schizophrenia—contribution of NMDA receptor development and hypofunction

Molecular Psychiatry, Journal Year: 2021, Volume and Issue: 27(1), P. 731 - 743

Published: June 23, 2021

Language: Английский

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Mature parvalbumin interneuron function in prefrontal cortex requires activity during a postnatal sensitive period

eLife, Journal Year: 2022, Volume and Issue: 11

Published: Dec. 28, 2022

In their seminal findings, Hubel and Wiesel identified sensitive periods in which experience can exert lasting effects on adult visual cortical functioning behavior via transient changes neuronal activity during development. Whether comparable exist for non-sensory cortices, such as the prefrontal cortex, alterations determine circuit function is still an active area of research. Here, using mice we demonstrate that inhibition parvalbumin (PV)-expressing interneurons juvenile adolescent period, results persistent impairments connectivity, vivo network function, behavioral flexibility be reversed by targeted activation PV adulthood. contrast, reversible suppression interneuron adulthood produces no effects. These findings identify activity-dependent period maturation highlight how abnormal development alters cognitive behavior.

Language: Английский

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Perinatal Hyperoxia and Developmental Consequences on the Lung-Brain Axis

Oxidative Medicine and Cellular Longevity, Journal Year: 2022, Volume and Issue: 2022, P. 1 - 17

Published: Feb. 24, 2022

Approximately 11.1% of all newborns worldwide are born preterm. Improved neonatal intensive care significantly increased survival rates over the last decades but failed to reduce risk for development chronic lung disease (i.e., bronchopulmonary dysplasia (BPD)) and impaired neurodevelopment encephalopathy prematurity (EoP)), two major long-term sequelae prematurity. Premature infants exposed relative hyperoxia, when compared physiological in-utero conditions and, if needed additional therapeutic oxygen supplementation. Both associated with an organ development. Since detrimental effects hyperoxia on immature retina known many years, brain have come into focus in decade. Hyperoxia-induced excessive production reactive species leading oxidative stress inflammation contribute pulmonary growth restriction abnormal neurodevelopment, including myelination deficits. Despite a large body studies, which unraveled important pathophysiological mechanisms both organs at risk, majority focused exclusively either or injury. However, considering that preterm suffering from BPD higher poor neurodevelopmental outcome, interaction between seems plausible. This review summarizes recent findings regarding hyperoxia-induced We will discuss common pathways, potentially link injured systems. Furthermore, promises needs currently suggested therapies, pharmacological regenerative cell-based treatments EoP, be emphasized. Limited approaches highlight urgent need better understanding underlying lung-brain axis order pave way novel multimodal ideally targeting severe birth-associated complications.

Language: Английский

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Neurodevelopmental disorders—high-resolution rethinking of disease modeling

Molecular Psychiatry, Journal Year: 2022, Volume and Issue: 28(1), P. 34 - 43

Published: Nov. 25, 2022

Abstract Neurodevelopmental disorders arise due to various risk factors that can perturb different stages of brain development, and a combinatorial impact these programs the phenotype in adulthood. While modeling complete neurodevelopmental disorder is challenging, individual developmental perturbations be successfully modeled vivo animals vitro human cellular models. Nevertheless, our limited knowledge development restricts strategies has raised questions how well model corresponds development. Recent progress high-resolution analysis tissue with single-cell spatial omics techniques enhanced understanding complex events govern health disease. This new utilized improve pave way more accurately portraying relevant disease

Language: Английский

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Reorganization of adolescent prefrontal cortex circuitry is required for mouse cognitive maturation

Neuron, Journal Year: 2023, Volume and Issue: 112(3), P. 421 - 440.e7

Published: Nov. 17, 2023

Most cognitive functions involving the prefrontal cortex emerge during late development. Increasing evidence links this delayed maturation to protracted timeline of development, which likely does not reach full maturity before end adolescence. However, underlying mechanisms that drive emergence and fine-tuning abilities adolescence, caused by circuit wiring, are still unknown. Here, we continuously monitored activity throughout postnatal development mice showed an initial increase was interrupted extensive microglia-mediated breakdown activity, followed rewiring elements achieve adult-like patterns synchrony. Interfering with these processes but adulthood, led a long-lasting microglia-induced disruption neuronal morphology decreased abilities. These results identified nonlinear reorganization circuits adolescence revealed its importance for adult network function processing.

Language: Английский

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