A role for endothelial NMDA receptors in the pathophysiology of schizophrenia
| Autor: | Katheron Intson, Amy J. Ramsey, Robert E. McCullumsmith, Salma Geissah |
|---|---|
| Rok vydání: | 2022 |
| Předmět: |
Postmortem studies
Glutamic Acid Receptors N-Methyl-D-Aspartate 03 medical and health sciences 0302 clinical medicine mental disorders Humans Medicine Premovement neuronal activity Receptor Biological Psychiatry Aspartic Acid business.industry musculoskeletal neural and ocular physiology Glutamate receptor Brain Neurovascular bundle Pathophysiology 030227 psychiatry Psychiatry and Mental health medicine.anatomical_structure nervous system Schizophrenia NMDA receptor Neuron business Neuroscience psychological phenomena and processes 030217 neurology & neurosurgery |
| Zdroj: | Schizophrenia Research. 249:63-73 |
| ISSN: | 0920-9964 |
| Popis: | Numerous genetic and postmortem studies link N-methyl-d-aspartate receptor (NMDAR) dysfunction with schizophrenia, forming the basis of the popular glutamate hypothesis. Neuronal NMDAR abnormalities are consistently reported from both basic and clinical experiments, however, non-neuronal cells also contain NMDARs, and are rarely, if ever, considered in the discussion of glutamate action in schizophrenia. We offer an examination of recent discoveries elucidating the actions and consequences of NMDAR activation in the neuroendothelium. While there has been mixed literature regarding blood flow alterations in the schizophrenia brain, in this review, we posit that some common findings may be explained by neuroendothelial NMDAR dysfunction. In particular, we emphasize that endothelial NMDARs are key mediators of neurovascular coupling, where increased neuronal activity leads to increased blood flow. Based on the broad conclusions that hypoperfusion is a neuroanatomical finding in schizophrenia, we discuss potential mechanisms by which endothelial NMDARs contribute to this disorder. We propose that endothelial NMDAR dysfunction can be a primary cause of neurovascular abnormalities in schizophrenia. Importantly, functional MRI studies using BOLD signal as a proxy for neuron activity should be considered in a new light if neurovascular coupling is impaired in schizophrenia. This review is the first to propose that NMDARs in non-excitable cells play a role in schizophrenia. |
| Databáze: | OpenAIRE |
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