ArticleSchizophrenia bulletin2021
Timely N-Acetyl-Cysteine and Environmental Enrichment Rescue Oxidative Stress-Induced Parvalbumin Interneuron Impairments via MMP9/RAGE Pathway: A Translational Approach for Early Intervention in Psychosis.
Article in Schizophrenia bulletin, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Linking Inflammation, Aberrant Glutamate-Dopamine Interaction, and Post-synaptic Changes: Translational Relevance for Schizophrenia and Antipsychotic Treatment: a Systematic Review.Molecular neurobiology · 2022Pooled it
- Maternal stressors disrupt mouse placental proteome and fetal brain development in a sex-specific fashion through inflammation and oxidative stress.Molecular psychiatry · 2025Article
- The antioxidant N-acetylcysteine prevents cortical neuropathological phenotypes caused by adolescent Δ-9-tetrahydrocannabinol exposure in male rats.Translational psychiatry · 2025Article
- Matrix Metalloproteinase Inhibitors and Their Potential Clinical Application in Periodontitis.Diseases (Basel, Switzerland) · 2025Review
- The Central Nervous System Modulatory Activities of N-Acetylcysteine: A Synthesis of Two Decades of Evidence.Current issues in molecular biology · 2025Review
- Sex-dependent preventive effects of prenatal N-acetyl-cysteine on neuronal, emotional and metabolic dysfunctions following exposure to maternal high-fat diet in mice.Translational psychiatry · 2025Article
- Protective Effects of N-Acetylcysteine Against Schizophrenia-Related Behavioral and Parvalbumin Interneuron Deficits Induced by Adolescent Stress.Schizophrenia bulletin open · 2025Article
- Matrix metalloproteinase 9 (MMP-9) activity, hippocampal extracellular free water, and cognitive deficits are associated with each other in early phase psychosis.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Article
- A bibliometric analysis of studies on environmental enrichment spanning 1967-2024: patterns and trends over the years.Frontiers in behavioral neuroscience · 2024Article
- Article
- Review: Genes Involved in Mitochondrial Physiology Within 22q11.2 Deleted Region and Their Relevance to Schizophrenia.Schizophrenia bulletin · 2023Article
- Redox and Immune Signaling in Schizophrenia: New Therapeutic Potential.The international journal of neuropsychopharmacology · 2023Review
- Hippocampal circuit dysfunction in psychosis.Translational psychiatry · 2022Review
- Chronic N-Acetylcysteine Treatment Prevents Amphetamine-Induced Hyperactivity in HeterozygousInternational journal of molecular sciences · 2022Article
- Caught in vicious circles: a perspective on dynamic feed-forward loops driving oxidative stress in schizophrenia.Molecular psychiatry · 2022Review
- At the Crossroad Between Resiliency and Fragility: A Neurodevelopmental Perspective on Early-Life Experiences.Frontiers in cellular neuroscience · 2022Review
- Chronic N-acetylcysteine treatment improves anhedonia and cognition in a mouse model of the schizophrenia prodrome.Frontiers in behavioral neuroscience · 2022Article
- The Antioxidant N-Acetyl-L-Cysteine Restores the Behavioral Deficits in a Neurodevelopmental Model of Schizophrenia Through a Mechanism That Involves Nitric Oxide.Frontiers in pharmacology · 2022Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Research in schizophrenia (SZ) emphasizes the need for new therapeutic approaches based on antioxidant/anti-inflammatory compounds and psycho-social therapy. A hallmark of SZ is a dysfunction of parvalbumin-expressing fast-spiking interneurons (PVI), which are essential for neuronal synchrony during sensory/cognitive processing. Oxidative stress and inflammation during early brain development, as observed in SZ, affect PVI maturation. We compared the efficacy of N-acetyl-cysteine (NAC) and/or environmental enrichment (EE) provided during juvenile and/or adolescent periods in rescuing PVI impairments induced by an additional oxidative insult during childhood in a transgenic mouse model with gluthation deficit (Gclm KO), relevant for SZ. We tested whether this rescue was promoted by the inhibition of MMP9/RAGE mechanism, both in the mouse model and in early psychosis (EP) patients, enrolled in a double-blind, randomized, placebo-controlled clinical trial of NAC supplementation for 6 months. We show that a sequential combination of NAC+EE applied after an early-life oxidative insult recovers integrity and function of PVI network in adult Gclm KO, via the inhibition of MMP9/RAGE. Six-month NAC treatment in EP patients reduces plasma sRAGE in association with increased prefrontal GABA, improvement of cognition and clinical symptoms, suggesting similar neuroprotective mechanisms. The sequential combination of NAC+EE reverses long-lasting effects of an early oxidative insult on PVI/perineuronal net (PNN) through the inhibition of MMP9/RAGE mechanism. In analogy, patients vulnerable to early-life insults could benefit from a combined pharmacological and psycho-social therapy.
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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.