Molecular aspects of glutamate dysregulation: implications for schizophrenia and its treatment
Open accessAbstract
The glutamate system is involved in many aspects of neuronal synaptic strength and function during development and throughout life. Synapse formation in early brain development, synapse maintenance, and synaptic plasticity are all influenced by the glutamate system. The number of neurons and the number of their connections are determined by the activity of the glutamate system and its receptors. Malfunctions of the glutamate system affect neuroplasticity and can cause neuronal toxicity. In schizophrenia, many glutamate-regulated processes seem to be perturbed. Abnormal neuronal development, abnormal synaptic plasticity, and neurodegeneration have been proposed to be causal or contributing factors in schizophrenia. Interestingly, it seems that the glutamate system is dysregulated and that N-methyl-D-aspartate receptors operate at reduced activity. Here we discuss how the molecular aspects of glutamate malfunction can explain some of the neuropathology observed in schizophrenia, and how the available treatment intervenes through the glutamate system.
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The high frequency of interneuron pathologies in the hippocampus and adjacent cortical areas, such as in schizophrenia and bipolar disorder, may partly reflect extended developmental vulnerability.
“The preponderance of interneuron pathologies in the hippocampus and adjacent cortical areas, such as the interneuron pathologies observed in schizophrenia and BPD, might be, at least in part, a reflection of this extended developmental vulnerability [1, 9, 122, 140-142].”
From Parvalbumin interneuron vulnerability and brain disorders (2021) · cites this paper as [122]
In schizophrenia, NMDA receptors are believed to be hypo-functioning, and NMDA receptor inhibition reproduces many schizophrenia symptoms.
“In schizophrenia, NMDA receptors are believed to be hypo-functioning, and the inhibition of NMDA receptors recapitulates many of the symptoms of schizophrenia [104, 122, 123].”
From Parvalbumin interneuron vulnerability and brain disorders (2021) · cites this paper as [122]
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References 386 · Cited by 336
Research works printed but not linked: 1
- Counihan TJ, Landwehrmeyer GB, Standaert DG, Kosinski CM, Scherzer CR, Daggett LP, Velicelebi G, Young AB, Penney JB., Jr. Expression of N-methyl-d-aspartate receptor subunit mRNA in the human brain: mesencephalic dopaminergic neurons. J Comp Neurol. 1998;390:91–101. [PubMed] [Google Scholar]
- Authors
- Konradi, C., & Heckers, S.
- Affiliations
- Harvard University (US)
- Corresponding author
- Konradi, Christine
- Venue
- Pharmacology & Therapeutics
- Publisher
- Elsevier BV
- Published
- 2003-02
- Volume
- 97
- Issue
- 2
- Pages
- 153-179
- ISSN
- 0163-7258 (ISSN-L)
- PMC
- PMC4203361
- OpenAlex
- W2035009272
- Cited by
- 336
- References
- 386
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 8 · 2023: 6 · 2022: 3 · 2021: 12 · 2020: 9 · 2019: 10 · 2018: 14 · 2017: 9 · 2016: 22 · 2015: 12 · 2014: 16 · 2013: 14 · 2012: 19
- FWCI
- 3.51
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Pharmacology & Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Drug Abuse (DA07134, R01DA007134)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Keywords
- glutamatergic system, schizophrenia, NMDA receptor, synaptic plasticity, neuroplasticity, neurodegeneration, neuronal development, glutamate receptors, glutamate dysregulation, antipsychotic drugs
- MeSH terms
- Glutamates, Humans, Schizophrenia, Antipsychotic Agents, Signal Transduction, Receptors, N-Methyl-D-Aspartate, Receptors, Glutamate, Neurotransmitter Agents
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