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Major Histocompatibility Complex class I proteins are critical for maintaining neuronal structural complexity in the aging brain

Major histocompatibility complex class I (MHCI) proteins have been implicated in neuronal function through the modulation of neuritogenesis, synaptogenesis, synaptic plasticity, and memory consolidation during development. However, the involvement of MHCI in the aged brain is unclear. Here we demons...

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Autores principales: Lazarczyk, Maciej J., Kemmler, Julia E., Eyford, Brett A., Short, Jennifer A., Varghese, Merina, Sowa, Allison, Dickstein, Daniel R., Yuk, Frank J., Puri, Rishi, Biron, Kaan E., Leist, Marcel, Jefferies, Wilfred A., Dickstein, Dara L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4882527/
https://www.ncbi.nlm.nih.gov/pubmed/27229916
http://dx.doi.org/10.1038/srep26199
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author Lazarczyk, Maciej J.
Kemmler, Julia E.
Eyford, Brett A.
Short, Jennifer A.
Varghese, Merina
Sowa, Allison
Dickstein, Daniel R.
Yuk, Frank J.
Puri, Rishi
Biron, Kaan E.
Leist, Marcel
Jefferies, Wilfred A.
Dickstein, Dara L.
author_facet Lazarczyk, Maciej J.
Kemmler, Julia E.
Eyford, Brett A.
Short, Jennifer A.
Varghese, Merina
Sowa, Allison
Dickstein, Daniel R.
Yuk, Frank J.
Puri, Rishi
Biron, Kaan E.
Leist, Marcel
Jefferies, Wilfred A.
Dickstein, Dara L.
author_sort Lazarczyk, Maciej J.
collection PubMed
description Major histocompatibility complex class I (MHCI) proteins have been implicated in neuronal function through the modulation of neuritogenesis, synaptogenesis, synaptic plasticity, and memory consolidation during development. However, the involvement of MHCI in the aged brain is unclear. Here we demonstrate that MHCI deficiency results in significant dendritic atrophy along with an increase in thin dendritic spines and a reduction in stubby spines in the hippocampus of aged (12 month old) mice. Ultrastructural analyses revealed a decrease in spine head diameter and post synaptic density (PSD) area, as well as an increase in overall synapse density, and non-perforated, small spines. Interestingly, we found that the changes in synapse density and morphology appear relatively late (after the age of 6 months). Finally, we found a significant age dependent increase in the levels of the glutamate receptor, GluN2B in aged MHCI knockout mice, with no change in GluA2/3, VGluT1, PSD95 or synaptophysin. These results indicate that MHCI may be also be involved in maintaining brain integrity at post-developmental stages notably in the modulation of neuronal and spine morphology and synaptic function during non-pathological aging which could have significant implications for cognitive function.
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spelling pubmed-48825272016-06-08 Major Histocompatibility Complex class I proteins are critical for maintaining neuronal structural complexity in the aging brain Lazarczyk, Maciej J. Kemmler, Julia E. Eyford, Brett A. Short, Jennifer A. Varghese, Merina Sowa, Allison Dickstein, Daniel R. Yuk, Frank J. Puri, Rishi Biron, Kaan E. Leist, Marcel Jefferies, Wilfred A. Dickstein, Dara L. Sci Rep Article Major histocompatibility complex class I (MHCI) proteins have been implicated in neuronal function through the modulation of neuritogenesis, synaptogenesis, synaptic plasticity, and memory consolidation during development. However, the involvement of MHCI in the aged brain is unclear. Here we demonstrate that MHCI deficiency results in significant dendritic atrophy along with an increase in thin dendritic spines and a reduction in stubby spines in the hippocampus of aged (12 month old) mice. Ultrastructural analyses revealed a decrease in spine head diameter and post synaptic density (PSD) area, as well as an increase in overall synapse density, and non-perforated, small spines. Interestingly, we found that the changes in synapse density and morphology appear relatively late (after the age of 6 months). Finally, we found a significant age dependent increase in the levels of the glutamate receptor, GluN2B in aged MHCI knockout mice, with no change in GluA2/3, VGluT1, PSD95 or synaptophysin. These results indicate that MHCI may be also be involved in maintaining brain integrity at post-developmental stages notably in the modulation of neuronal and spine morphology and synaptic function during non-pathological aging which could have significant implications for cognitive function. Nature Publishing Group 2016-05-27 /pmc/articles/PMC4882527/ /pubmed/27229916 http://dx.doi.org/10.1038/srep26199 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Lazarczyk, Maciej J.
Kemmler, Julia E.
Eyford, Brett A.
Short, Jennifer A.
Varghese, Merina
Sowa, Allison
Dickstein, Daniel R.
Yuk, Frank J.
Puri, Rishi
Biron, Kaan E.
Leist, Marcel
Jefferies, Wilfred A.
Dickstein, Dara L.
Major Histocompatibility Complex class I proteins are critical for maintaining neuronal structural complexity in the aging brain
title Major Histocompatibility Complex class I proteins are critical for maintaining neuronal structural complexity in the aging brain
title_full Major Histocompatibility Complex class I proteins are critical for maintaining neuronal structural complexity in the aging brain
title_fullStr Major Histocompatibility Complex class I proteins are critical for maintaining neuronal structural complexity in the aging brain
title_full_unstemmed Major Histocompatibility Complex class I proteins are critical for maintaining neuronal structural complexity in the aging brain
title_short Major Histocompatibility Complex class I proteins are critical for maintaining neuronal structural complexity in the aging brain
title_sort major histocompatibility complex class i proteins are critical for maintaining neuronal structural complexity in the aging brain
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4882527/
https://www.ncbi.nlm.nih.gov/pubmed/27229916
http://dx.doi.org/10.1038/srep26199
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