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The relationship between synaptic density marker SV2A, glutamate and N-acetyl aspartate levels in healthy volunteers and schizophrenia: a multimodal PET and magnetic resonance spectroscopy brain imaging study
Glutamatergic excitotoxicity is hypothesised to underlie synaptic loss in schizophrenia pathogenesis, but it is unknown whether synaptic markers are related to glutamatergic function in vivo. Additionally, it has been proposed that N-acetyl aspartate (NAA) levels reflect neuronal integrity. Here, we...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290006/ https://www.ncbi.nlm.nih.gov/pubmed/34282130 http://dx.doi.org/10.1038/s41398-021-01515-3 |
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author | Onwordi, Ellis Chika Whitehurst, Thomas Mansur, Ayla Statton, Ben Berry, Alaine Quinlan, Marina O’Regan, Declan P. Rogdaki, Maria Marques, Tiago Reis Rabiner, Eugenii A. Gunn, Roger N. Vernon, Anthony C. Natesan, Sridhar Howes, Oliver D. |
author_facet | Onwordi, Ellis Chika Whitehurst, Thomas Mansur, Ayla Statton, Ben Berry, Alaine Quinlan, Marina O’Regan, Declan P. Rogdaki, Maria Marques, Tiago Reis Rabiner, Eugenii A. Gunn, Roger N. Vernon, Anthony C. Natesan, Sridhar Howes, Oliver D. |
author_sort | Onwordi, Ellis Chika |
collection | PubMed |
description | Glutamatergic excitotoxicity is hypothesised to underlie synaptic loss in schizophrenia pathogenesis, but it is unknown whether synaptic markers are related to glutamatergic function in vivo. Additionally, it has been proposed that N-acetyl aspartate (NAA) levels reflect neuronal integrity. Here, we investigated whether synaptic vesicle glycoprotein 2 A (SV2A) levels are related to glutamatergic markers and NAA in healthy volunteers (HV) and schizophrenia patients (SCZ). Forty volunteers (SCZ n = 18, HV n = 22) underwent [(11)C]UCB-J positron emission tomography and proton magnetic resonance spectroscopy ((1)H-MRS) imaging in the left hippocampus and anterior cingulate cortex (ACC) to index [(11)C]UCB-J distribution volume ratio (DVR), and creatine-scaled glutamate (Glu/Cr), glutamate and glutamine (Glx/Cr) and NAA (NAA/Cr). In healthy volunteers, but not patients, [(11)C]UCB-J DVR was significantly positively correlated with Glu/Cr, in both the hippocampus and ACC. Furthermore, in healthy volunteers, but not patients, [(11)C]UCB-J DVR was significantly positively correlated with Glx/Cr, in both the hippocampus and ACC. There were no significant relationships between [(11)C]UCB-J DVR and NAA/Cr in the hippocampus or ACC in healthy volunteers or patients. Therefore, an appreciable proportion of the brain (1)H-MRS glutamatergic signal is related to synaptic density in healthy volunteers. This relationship is not seen in schizophrenia, which, taken with lower synaptic marker levels, is consistent with lower levels of glutamatergic terminals and/or a lower proportion of glutamatergic relative to GABAergic terminals in the ACC in schizophrenia. |
format | Online Article Text |
id | pubmed-8290006 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-82900062021-07-23 The relationship between synaptic density marker SV2A, glutamate and N-acetyl aspartate levels in healthy volunteers and schizophrenia: a multimodal PET and magnetic resonance spectroscopy brain imaging study Onwordi, Ellis Chika Whitehurst, Thomas Mansur, Ayla Statton, Ben Berry, Alaine Quinlan, Marina O’Regan, Declan P. Rogdaki, Maria Marques, Tiago Reis Rabiner, Eugenii A. Gunn, Roger N. Vernon, Anthony C. Natesan, Sridhar Howes, Oliver D. Transl Psychiatry Article Glutamatergic excitotoxicity is hypothesised to underlie synaptic loss in schizophrenia pathogenesis, but it is unknown whether synaptic markers are related to glutamatergic function in vivo. Additionally, it has been proposed that N-acetyl aspartate (NAA) levels reflect neuronal integrity. Here, we investigated whether synaptic vesicle glycoprotein 2 A (SV2A) levels are related to glutamatergic markers and NAA in healthy volunteers (HV) and schizophrenia patients (SCZ). Forty volunteers (SCZ n = 18, HV n = 22) underwent [(11)C]UCB-J positron emission tomography and proton magnetic resonance spectroscopy ((1)H-MRS) imaging in the left hippocampus and anterior cingulate cortex (ACC) to index [(11)C]UCB-J distribution volume ratio (DVR), and creatine-scaled glutamate (Glu/Cr), glutamate and glutamine (Glx/Cr) and NAA (NAA/Cr). In healthy volunteers, but not patients, [(11)C]UCB-J DVR was significantly positively correlated with Glu/Cr, in both the hippocampus and ACC. Furthermore, in healthy volunteers, but not patients, [(11)C]UCB-J DVR was significantly positively correlated with Glx/Cr, in both the hippocampus and ACC. There were no significant relationships between [(11)C]UCB-J DVR and NAA/Cr in the hippocampus or ACC in healthy volunteers or patients. Therefore, an appreciable proportion of the brain (1)H-MRS glutamatergic signal is related to synaptic density in healthy volunteers. This relationship is not seen in schizophrenia, which, taken with lower synaptic marker levels, is consistent with lower levels of glutamatergic terminals and/or a lower proportion of glutamatergic relative to GABAergic terminals in the ACC in schizophrenia. Nature Publishing Group UK 2021-07-17 /pmc/articles/PMC8290006/ /pubmed/34282130 http://dx.doi.org/10.1038/s41398-021-01515-3 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Onwordi, Ellis Chika Whitehurst, Thomas Mansur, Ayla Statton, Ben Berry, Alaine Quinlan, Marina O’Regan, Declan P. Rogdaki, Maria Marques, Tiago Reis Rabiner, Eugenii A. Gunn, Roger N. Vernon, Anthony C. Natesan, Sridhar Howes, Oliver D. The relationship between synaptic density marker SV2A, glutamate and N-acetyl aspartate levels in healthy volunteers and schizophrenia: a multimodal PET and magnetic resonance spectroscopy brain imaging study |
title | The relationship between synaptic density marker SV2A, glutamate and N-acetyl aspartate levels in healthy volunteers and schizophrenia: a multimodal PET and magnetic resonance spectroscopy brain imaging study |
title_full | The relationship between synaptic density marker SV2A, glutamate and N-acetyl aspartate levels in healthy volunteers and schizophrenia: a multimodal PET and magnetic resonance spectroscopy brain imaging study |
title_fullStr | The relationship between synaptic density marker SV2A, glutamate and N-acetyl aspartate levels in healthy volunteers and schizophrenia: a multimodal PET and magnetic resonance spectroscopy brain imaging study |
title_full_unstemmed | The relationship between synaptic density marker SV2A, glutamate and N-acetyl aspartate levels in healthy volunteers and schizophrenia: a multimodal PET and magnetic resonance spectroscopy brain imaging study |
title_short | The relationship between synaptic density marker SV2A, glutamate and N-acetyl aspartate levels in healthy volunteers and schizophrenia: a multimodal PET and magnetic resonance spectroscopy brain imaging study |
title_sort | relationship between synaptic density marker sv2a, glutamate and n-acetyl aspartate levels in healthy volunteers and schizophrenia: a multimodal pet and magnetic resonance spectroscopy brain imaging study |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290006/ https://www.ncbi.nlm.nih.gov/pubmed/34282130 http://dx.doi.org/10.1038/s41398-021-01515-3 |
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