ArticleNeurobiology of learning and memory2017
Juvenile treatment with a novel mGluR2 agonist/mGluR3 antagonist compound, LY395756, reverses learning deficits and cognitive flexibility impairments in adults in a neurodevelopmental model of schizophrenia.
Article in Neurobiology of learning and memory, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 18 citations in OpenAlex.
- TMEM16A ablation in cholinergic medial habenula neurons induces early-onset schizophrenia-like phenotypes in mice.Molecular brain · 2026Article
- How to Improve Cognitive Flexibility: Evidence From Noninvasive Neuromodulation Techniques.CNS neuroscience & therapeutics · 2025Review
- Exploring the Potential of Probiotics and Prebiotics in Major Depression: From Molecular Function to Clinical Therapy.Probiotics and antimicrobial proteins · 2024Review
- Attenuation of Stimulated Accumbal Dopamine Release by NMDA Is Mediated through Metabotropic Glutamate Receptors.ACS chemical neuroscience · 2023Article
- Animal Models of Relevance to the Schizophrenia Prodrome.Biological psychiatry global open science · 2023Review
- The role of thalamic group II mGlu receptors in health and disease.Neuronal signaling · 2022Review
- LY395756 promotes NR2B expression via activation of AKT/CREB signaling in the juvenile methylazoxymethanol mice model of schizophrenia.Brain and behavior · 2022Article
- Aberrant maturation and connectivity of prefrontal cortex in schizophrenia-contribution of NMDA receptor development and hypofunction.Molecular psychiatry · 2022Review
- Anti-anxiety and antidepressant-like effects of astragaloside IV and saponins extracted from Astragalus spinosus against the bisphenol A-induced motor and cognitive impairments in a postnatal rat model of schizophrenia.Environmental science and pollution research international · 2021Article
- The G Protein-Coupled Glutamate Receptors as Novel Molecular Targets in Schizophrenia Treatment-A Narrative Review.Journal of clinical medicine · 2021Review
- NMDA receptor hypofunction for schizophrenia revisited: Perspectives from epigenetic mechanisms.Schizophrenia research · 2020Review
- Juvenile treatment with mGluR2/3 agonist prevents schizophrenia-like phenotypes in adult by acting through GSK3β.Neuropharmacology · 2018Article
- Review
- Epigenetic mechanisms underlying NMDA receptor hypofunction in the prefrontal cortex of juvenile animals in the MAM model for schizophrenia.Journal of neurochemistry · 2017Article
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Schizophrenia (SCZ) is a neurodevelopmental psychiatric disorder, in which cognitive function becomes disrupted at early stages of the disease. Although the mechanisms underlying cognitive impairments remain unclear, N-methyl-D-aspartate receptors (NMDAR) hypofunctioning in the prefrontal cortex (PFC) has been implicated. Moreover, cognitive symptoms in SCZ are usually unresponsive to treatment with current antipsychotics and by onset, disruption of the dopamine system, not NMDAR hypofunctioning, dominates the symptoms. Therefore, treating cognitive deficits at an early stage is a realistic approach. In this study, we tested whether an early treatment targeting mGluR2 would be effective in ameliorating cognitive impairments in the methylazoxymethanol acetate (MAM) model of SCZ. We investigated the effects of an mGluR2 agonist/mGluR3 antagonist, LY395756 (LY39), on the NMDAR expression and function in juveniles, as well as cognitive deficits in adult rats after juvenile treatment. We found that gestational MAM exposure induced a significant decrease in total protein levels of the NMDAR subunit, NR2B, and a significant increase of pNR2BTyr1472 in the juvenile rat PFC. Treatment with LY39 in juvenile MAM-exposed rats effectively recovered the disrupted NMDAR expression. Furthermore, a subchronic LY39 treatment in juvenile MAM-exposed rats also alleviated the learning deficits and cognitive flexibility impairments when tested with a cross-maze based set-shifting task in adults. Therefore, our study demonstrates that targeting dysfunctional NMDARs with an mGluR2 agonist during the early stage of SCZ could be an effective strategy in preventing the development and progression in addition to ameliorating cognitive impairments of SCZ.
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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.