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The “Loss” of Perineuronal Nets in Alzheimer's Disease: Missing or Hiding in Plain Sight?

Perineuronal nets (PNNs) are chondroitin-sulfate glycosaminoglycan (CS-GAG) containing extracellular matrix structures that assemble around neurons involved in learning, memory, and cognition. Owing to the unique patterning of negative charges stemming from sulfate modifications to the attached CS-G...

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Autores principales: Scarlett, Jarrad M., Hu, Shannon J., Alonge, Kimberly M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9174696/
https://www.ncbi.nlm.nih.gov/pubmed/35694184
http://dx.doi.org/10.3389/fnint.2022.896400
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author Scarlett, Jarrad M.
Hu, Shannon J.
Alonge, Kimberly M.
author_facet Scarlett, Jarrad M.
Hu, Shannon J.
Alonge, Kimberly M.
author_sort Scarlett, Jarrad M.
collection PubMed
description Perineuronal nets (PNNs) are chondroitin-sulfate glycosaminoglycan (CS-GAG) containing extracellular matrix structures that assemble around neurons involved in learning, memory, and cognition. Owing to the unique patterning of negative charges stemming from sulfate modifications to the attached CS-GAGs, these matrices play key roles in mediating glycan-protein binding, signaling interactions, and charged ion buffering of the underlying circuitry. Histochemical loss of PNN matrices has been reported for a range of neurocognitive and neurodegenerative diseases, implying that PNNs might be a key player in the pathogenesis of neurological disorders. In this hypothesis and theory article, we begin by highlighting PNN changes observed in human postmortem brain tissue associated with Alzheimer's disease (AD) and corresponding changes reported in rodent models of AD neuropathology. We then discuss the technical limitations surrounding traditional methods for PNN analyses and propose alternative explanations to these historical findings. Lastly, we embark on a global re-evaluation of the interpretations for PNN changes across brain regions, across species, and in relation to other neurocognitive disorders.
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spelling pubmed-91746962022-06-09 The “Loss” of Perineuronal Nets in Alzheimer's Disease: Missing or Hiding in Plain Sight? Scarlett, Jarrad M. Hu, Shannon J. Alonge, Kimberly M. Front Integr Neurosci Neuroscience Perineuronal nets (PNNs) are chondroitin-sulfate glycosaminoglycan (CS-GAG) containing extracellular matrix structures that assemble around neurons involved in learning, memory, and cognition. Owing to the unique patterning of negative charges stemming from sulfate modifications to the attached CS-GAGs, these matrices play key roles in mediating glycan-protein binding, signaling interactions, and charged ion buffering of the underlying circuitry. Histochemical loss of PNN matrices has been reported for a range of neurocognitive and neurodegenerative diseases, implying that PNNs might be a key player in the pathogenesis of neurological disorders. In this hypothesis and theory article, we begin by highlighting PNN changes observed in human postmortem brain tissue associated with Alzheimer's disease (AD) and corresponding changes reported in rodent models of AD neuropathology. We then discuss the technical limitations surrounding traditional methods for PNN analyses and propose alternative explanations to these historical findings. Lastly, we embark on a global re-evaluation of the interpretations for PNN changes across brain regions, across species, and in relation to other neurocognitive disorders. Frontiers Media S.A. 2022-05-25 /pmc/articles/PMC9174696/ /pubmed/35694184 http://dx.doi.org/10.3389/fnint.2022.896400 Text en Copyright © 2022 Scarlett, Hu and Alonge. 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
Scarlett, Jarrad M.
Hu, Shannon J.
Alonge, Kimberly M.
The “Loss” of Perineuronal Nets in Alzheimer's Disease: Missing or Hiding in Plain Sight?
title The “Loss” of Perineuronal Nets in Alzheimer's Disease: Missing or Hiding in Plain Sight?
title_full The “Loss” of Perineuronal Nets in Alzheimer's Disease: Missing or Hiding in Plain Sight?
title_fullStr The “Loss” of Perineuronal Nets in Alzheimer's Disease: Missing or Hiding in Plain Sight?
title_full_unstemmed The “Loss” of Perineuronal Nets in Alzheimer's Disease: Missing or Hiding in Plain Sight?
title_short The “Loss” of Perineuronal Nets in Alzheimer's Disease: Missing or Hiding in Plain Sight?
title_sort “loss” of perineuronal nets in alzheimer's disease: missing or hiding in plain sight?
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9174696/
https://www.ncbi.nlm.nih.gov/pubmed/35694184
http://dx.doi.org/10.3389/fnint.2022.896400
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