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A Preliminary Report: The Hippocampus and Surrounding Temporal Cortex of Patients With Schizophrenia Have Impaired Blood-Brain Barrier

Though hippocampal volume reduction is a pathological hallmark of schizophrenia, the molecular pathway(s) responsible for this degeneration remains unknown. Recent reports have suggested the potential role of impaired blood-brain barrier (BBB) function in schizophrenia pathogenesis. However, direct...

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Autores principales: Goldwaser, Eric L., Swanson, Randel L., Arroyo, Edgardo J., Venkataraman, Venkat, Kosciuk, Mary C., Nagele, Robert G., Hong, L. Elliot, Acharya, Nimish K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9008835/
https://www.ncbi.nlm.nih.gov/pubmed/35431844
http://dx.doi.org/10.3389/fnhum.2022.836980
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author Goldwaser, Eric L.
Swanson, Randel L.
Arroyo, Edgardo J.
Venkataraman, Venkat
Kosciuk, Mary C.
Nagele, Robert G.
Hong, L. Elliot
Acharya, Nimish K.
author_facet Goldwaser, Eric L.
Swanson, Randel L.
Arroyo, Edgardo J.
Venkataraman, Venkat
Kosciuk, Mary C.
Nagele, Robert G.
Hong, L. Elliot
Acharya, Nimish K.
author_sort Goldwaser, Eric L.
collection PubMed
description Though hippocampal volume reduction is a pathological hallmark of schizophrenia, the molecular pathway(s) responsible for this degeneration remains unknown. Recent reports have suggested the potential role of impaired blood-brain barrier (BBB) function in schizophrenia pathogenesis. However, direct evidence demonstrating an impaired BBB function is missing. In this preliminary study, we used immunohistochemistry and serum immunoglobulin G (IgG) antibodies to investigate the state of BBB function in formalin-fixed postmortem samples from the hippocampus and surrounding temporal cortex of patients with schizophrenia (n = 25) and controls without schizophrenia (n = 27) matched for age, sex, and race. Since a functional BBB prevents the extravasation of IgGs, detection of IgGs in the parenchyma is used as direct evidence of BBB breakdown. We also developed a semi-quantitative approach to quantify the extent of IgG leak and therein BBB breach. Analysis of our immunohistochemistry data demonstrated a significantly higher incidence of IgG leak in patients with schizophrenia compared to controls. Further, BBB permeability was significantly higher in advanced-age patients with schizophrenia than both advanced-age controls and middle-aged patients with schizophrenia. Male patients with schizophrenia also demonstrated a significant increase in IgG permeability compared to control males. Interestingly, the extravasated IgGs also demonstrated selective immunoreactivity for neurons. Based on these observations, we suggest that BBB dysfunction and IgG autoantibodies could be two key missing pathoetiological links underwriting schizophrenia hippocampal damage.
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spelling pubmed-90088352022-04-15 A Preliminary Report: The Hippocampus and Surrounding Temporal Cortex of Patients With Schizophrenia Have Impaired Blood-Brain Barrier Goldwaser, Eric L. Swanson, Randel L. Arroyo, Edgardo J. Venkataraman, Venkat Kosciuk, Mary C. Nagele, Robert G. Hong, L. Elliot Acharya, Nimish K. Front Hum Neurosci Neuroscience Though hippocampal volume reduction is a pathological hallmark of schizophrenia, the molecular pathway(s) responsible for this degeneration remains unknown. Recent reports have suggested the potential role of impaired blood-brain barrier (BBB) function in schizophrenia pathogenesis. However, direct evidence demonstrating an impaired BBB function is missing. In this preliminary study, we used immunohistochemistry and serum immunoglobulin G (IgG) antibodies to investigate the state of BBB function in formalin-fixed postmortem samples from the hippocampus and surrounding temporal cortex of patients with schizophrenia (n = 25) and controls without schizophrenia (n = 27) matched for age, sex, and race. Since a functional BBB prevents the extravasation of IgGs, detection of IgGs in the parenchyma is used as direct evidence of BBB breakdown. We also developed a semi-quantitative approach to quantify the extent of IgG leak and therein BBB breach. Analysis of our immunohistochemistry data demonstrated a significantly higher incidence of IgG leak in patients with schizophrenia compared to controls. Further, BBB permeability was significantly higher in advanced-age patients with schizophrenia than both advanced-age controls and middle-aged patients with schizophrenia. Male patients with schizophrenia also demonstrated a significant increase in IgG permeability compared to control males. Interestingly, the extravasated IgGs also demonstrated selective immunoreactivity for neurons. Based on these observations, we suggest that BBB dysfunction and IgG autoantibodies could be two key missing pathoetiological links underwriting schizophrenia hippocampal damage. Frontiers Media S.A. 2022-03-31 /pmc/articles/PMC9008835/ /pubmed/35431844 http://dx.doi.org/10.3389/fnhum.2022.836980 Text en Copyright © 2022 Goldwaser, Swanson, Arroyo, Venkataraman, Kosciuk, Nagele, Hong and Acharya. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Neuroscience
Goldwaser, Eric L.
Swanson, Randel L.
Arroyo, Edgardo J.
Venkataraman, Venkat
Kosciuk, Mary C.
Nagele, Robert G.
Hong, L. Elliot
Acharya, Nimish K.
A Preliminary Report: The Hippocampus and Surrounding Temporal Cortex of Patients With Schizophrenia Have Impaired Blood-Brain Barrier
title A Preliminary Report: The Hippocampus and Surrounding Temporal Cortex of Patients With Schizophrenia Have Impaired Blood-Brain Barrier
title_full A Preliminary Report: The Hippocampus and Surrounding Temporal Cortex of Patients With Schizophrenia Have Impaired Blood-Brain Barrier
title_fullStr A Preliminary Report: The Hippocampus and Surrounding Temporal Cortex of Patients With Schizophrenia Have Impaired Blood-Brain Barrier
title_full_unstemmed A Preliminary Report: The Hippocampus and Surrounding Temporal Cortex of Patients With Schizophrenia Have Impaired Blood-Brain Barrier
title_short A Preliminary Report: The Hippocampus and Surrounding Temporal Cortex of Patients With Schizophrenia Have Impaired Blood-Brain Barrier
title_sort preliminary report: the hippocampus and surrounding temporal cortex of patients with schizophrenia have impaired blood-brain barrier
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9008835/
https://www.ncbi.nlm.nih.gov/pubmed/35431844
http://dx.doi.org/10.3389/fnhum.2022.836980
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