Journal article
NMDA hypofunction as a convergence point for progression and symptoms of schizophrenia
Frontiers in cellular neuroscience, v 7, pp 31-31
27 Mar 2013
PMID: 23543703
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Schizophrenia is a disabling mental illness that is now recognized as a neurodevelopmental disorder. It is likely that genetic risk factors interact with environmental perturbations to affect normal brain development and that this altered trajectory results in a combination of positive, negative, and cognitive symptoms. Although the exact pathophysiology of schizophrenia is unknown, the N-methyl-D-aspartate receptor (NMDAR), a major glutamate receptor subtype, has received great attention. Proper expression and regulation of NMDARs in the brain is critical for learning and memory processes as well as cortical plasticity and maturation. Evidence from both animal models and human studies implicates a dysfunction of NMDARs both in disease progression and symptoms of schizophrenia. Furthermore, mutations in many of the known genetic risk factors for schizophrenia suggest that NMDAR hypofunction is a convergence point for schizophrenia. In this review, we discuss how disrupted NMDAR function leads to altered neurodevelopment that may contribute to the progression and development of symptoms for schizophrenia, particularly cognitive deficits. We review the shared signaling pathways among the schizophrenia susceptibility genes DISC1, neuregulin1, and dysbindin, focusing on the AKT/GSK3β pathway, and how their mutations and interactions can lead to NMDAR dysfunction during development. Additionally, we explore what open questions remain and suggest where schizophrenia research needs to move in order to provide mechanistic insight into the cause of NMDAR dysfunction, as well as generate possible new avenues for therapeutic intervention.
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Details
- Title
- NMDA hypofunction as a convergence point for progression and symptoms of schizophrenia
- Creators
- Melissa A SnyderWen-Jun Gao
- Publication Details
- Frontiers in cellular neuroscience, v 7, pp 31-31
- Publisher
- Frontiers Media S.A
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Neurobiology and Anatomy
- Web of Science ID
- WOS:000316938000001
- Scopus ID
- 2-s2.0-84875952213
- Other Identifier
- 991014877713704721
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- Web of Science research areas
- Neurosciences