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Journal article
Juvenile treatment with mGluR2/3 agonist prevents schizophrenia-like phenotypes in adult by acting through GSK3 beta
Neuropharmacology, v 137, pp 359-371
15 Jul 2018
PMCID: PMC6050107
PMID: 29793154
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Prodromal memory deficits represent an important marker for the development of schizophrenia (SZ), in which glutamatergic hypofunction occurs in the prefrontal cortex (PFC). The mGluR2/3 agonist LY379268 (LY37) attenuates excitatory N-methyl-D-aspartate receptor (NMDAR)-induced neurotoxicity, a central pathological characteristic of glutamatergic hypofunction. We therefore hypothesized that early treatment with LY37 would rescue cognitive deficits and confer benefits for SZ-like behaviors in adults. To test this, we assessed whether early intervention with LY37 would improve learning outcomes in the Morris Water Maze for rats prenatally exposed to methylazoxymethanol acetate (MAM), a neurodevelopmental SZ model. We found that a medium dose of LY37 prevents learning deficits in MAM rats. These effects were mediated through postsynaptic mGluR2/3 via improving GIuN2B-NMDAR function by inhibiting glycogen synthase kinase-3 beta (GSK3 beta). Furthermore, dendritic spine loss and learning and memory deficits observed in adult MAM rats were restored by juvenile LY37 treatment, which did not change prefrontal neuronal excitability and glutamatergic synaptic transmission in adult normal rats. Our results provide a mechanism for mGluR2/3 agonists against NMDAR hypofunction, which may prove to be beneficial in the prophylactic treatment of SZ. (C) 2018 Elsevier Ltd. All rights reserved.
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Details
- Title
- Juvenile treatment with mGluR2/3 agonist prevents schizophrenia-like phenotypes in adult by acting through GSK3 beta
- Creators
- Bo Xing - Drexel UniversityGenie Han - Drexel UniversityMin Juan Wang - Drexel UniversityMelissa A. Snyder - Drexel UniversityWen Jun Gao - Drexel University
- Publication Details
- Neuropharmacology, v 137, pp 359-371
- Publisher
- Elsevier
- Number of pages
- 13
- Grant note
- R01MH085666 / NATIONAL INSTITUTE OF MENTAL HEALTH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Mental Health (NIMH) R01MH085666; R21MH110678 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA NARSAD Independent Award 2015 4100072545 / Pennsylvania Commonwealth (CURE 2016)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Decision Sciences (and Management Information Systems); Neurobiology and Anatomy
- Web of Science ID
- WOS:000440776100032
- Scopus ID
- 2-s2.0-85047973461
- Other Identifier
- 991019302291404721
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Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Neurosciences
- Pharmacology & Pharmacy