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Synaptic loss in a mouse model of euthyroid Hashimoto’s thyroiditis: possible involvement of the microglia
BACKGROUND: Hashimoto’s thyroiditis (HT) is an autoimmune illness that renders individuals vulnerable to neuropsychopathology even in the euthyroid state, the mechanisms involved remain unclear. We hypothesized that activated microglia might disrupt synapses, resulting in cognitive disturbance in th...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9036731/ https://www.ncbi.nlm.nih.gov/pubmed/35468730 http://dx.doi.org/10.1186/s12868-022-00710-2 |
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author | Wang, Fen Cai, Yao-Jun Ma, Xiao Wang, Nan Wu, Zhang-Bi Sun, Yan Xu, Yong-xia Yang, Hao Liu, Tian-tian Xia, Qin Yu, Zhen Zhu, De-Fa |
author_facet | Wang, Fen Cai, Yao-Jun Ma, Xiao Wang, Nan Wu, Zhang-Bi Sun, Yan Xu, Yong-xia Yang, Hao Liu, Tian-tian Xia, Qin Yu, Zhen Zhu, De-Fa |
author_sort | Wang, Fen |
collection | PubMed |
description | BACKGROUND: Hashimoto’s thyroiditis (HT) is an autoimmune illness that renders individuals vulnerable to neuropsychopathology even in the euthyroid state, the mechanisms involved remain unclear. We hypothesized that activated microglia might disrupt synapses, resulting in cognitive disturbance in the context of euthyroid HT, and designed the present study to test this hypothesis. METHODS: Experimental HT model was induced by immunizing NOD mice with thyroglobulin and adjuvant twice. Morris Water Maze was measured to determine mice spatial learning and memory. The synaptic parameters such as the synaptic density, synaptic ultrastructure and synaptic-markers (SYN and PSD95) as well as the interactions of microglia with synapses were also determined. RESULTS: HT mice had poorer performance in Morris Water Maze than controls. Concurrently, HT resulted in a significant reduction in synapse density and ultrastructure damage, along with decreased synaptic puncta visualized by immunostaining with synaptophysin and PSD-95. In parallel, frontal activated microglia in euthyroid HT mice showed increased engulfment of PSD95 and EM revealed that the synaptic structures were visible within the microglia. These functional alterations in microglia corresponded to structural increases in their attachment to neuronal perikarya and a reduction in presynaptic terminals covering the neurons. CONCLUSION: Our results provide initial evidence that HT can induce synaptic loss in the euthyroid state with deficits might be attributable to activated microglia, which may underlie the deleterious effects of HT on spatial learning and memory. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12868-022-00710-2. |
format | Online Article Text |
id | pubmed-9036731 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-90367312022-04-26 Synaptic loss in a mouse model of euthyroid Hashimoto’s thyroiditis: possible involvement of the microglia Wang, Fen Cai, Yao-Jun Ma, Xiao Wang, Nan Wu, Zhang-Bi Sun, Yan Xu, Yong-xia Yang, Hao Liu, Tian-tian Xia, Qin Yu, Zhen Zhu, De-Fa BMC Neurosci Research BACKGROUND: Hashimoto’s thyroiditis (HT) is an autoimmune illness that renders individuals vulnerable to neuropsychopathology even in the euthyroid state, the mechanisms involved remain unclear. We hypothesized that activated microglia might disrupt synapses, resulting in cognitive disturbance in the context of euthyroid HT, and designed the present study to test this hypothesis. METHODS: Experimental HT model was induced by immunizing NOD mice with thyroglobulin and adjuvant twice. Morris Water Maze was measured to determine mice spatial learning and memory. The synaptic parameters such as the synaptic density, synaptic ultrastructure and synaptic-markers (SYN and PSD95) as well as the interactions of microglia with synapses were also determined. RESULTS: HT mice had poorer performance in Morris Water Maze than controls. Concurrently, HT resulted in a significant reduction in synapse density and ultrastructure damage, along with decreased synaptic puncta visualized by immunostaining with synaptophysin and PSD-95. In parallel, frontal activated microglia in euthyroid HT mice showed increased engulfment of PSD95 and EM revealed that the synaptic structures were visible within the microglia. These functional alterations in microglia corresponded to structural increases in their attachment to neuronal perikarya and a reduction in presynaptic terminals covering the neurons. CONCLUSION: Our results provide initial evidence that HT can induce synaptic loss in the euthyroid state with deficits might be attributable to activated microglia, which may underlie the deleterious effects of HT on spatial learning and memory. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12868-022-00710-2. BioMed Central 2022-04-25 /pmc/articles/PMC9036731/ /pubmed/35468730 http://dx.doi.org/10.1186/s12868-022-00710-2 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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 licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence 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 licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Wang, Fen Cai, Yao-Jun Ma, Xiao Wang, Nan Wu, Zhang-Bi Sun, Yan Xu, Yong-xia Yang, Hao Liu, Tian-tian Xia, Qin Yu, Zhen Zhu, De-Fa Synaptic loss in a mouse model of euthyroid Hashimoto’s thyroiditis: possible involvement of the microglia |
title | Synaptic loss in a mouse model of euthyroid Hashimoto’s thyroiditis: possible involvement of the microglia |
title_full | Synaptic loss in a mouse model of euthyroid Hashimoto’s thyroiditis: possible involvement of the microglia |
title_fullStr | Synaptic loss in a mouse model of euthyroid Hashimoto’s thyroiditis: possible involvement of the microglia |
title_full_unstemmed | Synaptic loss in a mouse model of euthyroid Hashimoto’s thyroiditis: possible involvement of the microglia |
title_short | Synaptic loss in a mouse model of euthyroid Hashimoto’s thyroiditis: possible involvement of the microglia |
title_sort | synaptic loss in a mouse model of euthyroid hashimoto’s thyroiditis: possible involvement of the microglia |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9036731/ https://www.ncbi.nlm.nih.gov/pubmed/35468730 http://dx.doi.org/10.1186/s12868-022-00710-2 |
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