Abstract:
: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.
journal_name
Schizophr Resjournal_title
Schizophrenia researchauthors
Intson K,Geissah S,McCullumsmith RE,Ramsey AJdoi
10.1016/j.schres.2020.10.004subject
Has Abstractpub_date
2020-11-11 00:00:00eissn
0920-9964issn
1573-2509pii
S0920-9964(20)30491-6pub_type
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pub_type: 杂志文章,随机对照试验
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更新日期:2014-06-01 00:00:00
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pub_type: 杂志文章
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更新日期:2018-12-01 00:00:00
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pub_type: 杂志文章,多中心研究,随机对照试验
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更新日期:2016-07-01 00:00:00
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pub_type: 杂志文章,多中心研究
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更新日期:2018-09-01 00:00:00
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pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章,评审
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pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章
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pub_type: 杂志文章,随机对照试验
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