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Journal article
PSD-95 deficiency disrupts PFC-associated function and behavior during neurodevelopment
Scientific reports, v 9(Jul (E-published)), pp 9486-13
01 Jul 2019
PMID: 31263190
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Postsynaptic density protein-95 (PSD-95) is a major regulator in the maturation of excitatory synapses by interacting and trafficking N-methyl-D-aspartic acid receptors (NMDAR) and α-amino-3-hydroxy-5-methyl-4-isox-azoleproprionic acid receptors (AMPAR) to the postsynaptic membrane. PSD-95 disruption has recently been associated with neuropsychiatric disorders such as schizophrenia and autism. However, the effects of PSD-95 deficiency on the prefrontal cortex (PFC)-associated functions, including cognition, working memory, and sociability, has yet to be investigated. Using a PSD-95 knockout mouse model (PSD-95
−/−
), we examined how PSD-95 deficiency affects NMDAR and AMPAR expression and function in the medial prefrontal cortex (mPFC) during juvenile and adolescent periods of development. We found significant increases in total protein levels of NMDAR subunits GluN1, and GluN2B, accompanied by decreases in AMPAR subunit GluA1 during adolescence. Correspondingly, there is a significant increase in NMDAR/AMPAR-mediated current amplitude ratio that progresses from juvenile-to-adolescence. Behaviorally, PSD-95
−/−
mice exhibit a lack of sociability, as well as learning and working memory deficits. Together, our data indicate that PSD-95 deficiency disrupts mPFC synaptic function and related behavior at a critical age of development. This study highlights the importance of PSD-95 during neurodevelopment in the mPFC and its potential link in the pathogenesis associated with schizophrenia and/or autism.
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Details
- Title
- PSD-95 deficiency disrupts PFC-associated function and behavior during neurodevelopment
- Creators
- Austin A. Coley - Drexel UniversityWen-Jun Gao - Drexel University
- Publication Details
- Scientific reports, v 9(Jul (E-published)), pp 9486-13
- Publisher
- Nature Publishing Group UK
- Grant note
- R01MH085666 / ; NINDS F99NS105185 / ;
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000473294100073
- Scopus ID
- 2-s2.0-85068251930
- Other Identifier
- 991019167589904721
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Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Neurosciences