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Altered hippocampal gene expression, glial cell population, and neuronal excitability in aminopeptidase P1 deficiency
Inborn errors of metabolism are often associated with neurodevelopmental disorders and brain injury. A deficiency of aminopeptidase P1, a proline-specific endopeptidase encoded by the Xpnpep1 gene, causes neurological complications in both humans and mice. In addition, aminopeptidase P1-deficient mi...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806765/ https://www.ncbi.nlm.nih.gov/pubmed/33441619 http://dx.doi.org/10.1038/s41598-020-79656-6 |
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author | Yoon, Sang Ho Bae, Young-Soo Oh, Sung Pyo Song, Woo Seok Chang, Hanna Kim, Myoung-Hwan |
author_facet | Yoon, Sang Ho Bae, Young-Soo Oh, Sung Pyo Song, Woo Seok Chang, Hanna Kim, Myoung-Hwan |
author_sort | Yoon, Sang Ho |
collection | PubMed |
description | Inborn errors of metabolism are often associated with neurodevelopmental disorders and brain injury. A deficiency of aminopeptidase P1, a proline-specific endopeptidase encoded by the Xpnpep1 gene, causes neurological complications in both humans and mice. In addition, aminopeptidase P1-deficient mice exhibit hippocampal neurodegeneration and impaired hippocampus-dependent learning and memory. However, the molecular and cellular changes associated with hippocampal pathology in aminopeptidase P1 deficiency are unclear. We show here that a deficiency of aminopeptidase P1 modifies the glial population and neuronal excitability in the hippocampus. Microarray and real-time quantitative reverse transcription-polymerase chain reaction analyses identified 14 differentially expressed genes (Casp1, Ccnd1, Myoc, Opalin, Aldh1a2, Aspa, Spp1, Gstm6, Serpinb1a, Pdlim1, Dsp, Tnfaip6, Slc6a20a, Slc22a2) in the Xpnpep1(−/−) hippocampus. In the hippocampus, aminopeptidase P1-expression signals were mainly detected in neurons. However, deficiency of aminopeptidase P1 resulted in fewer hippocampal astrocytes and increased density of microglia in the hippocampal CA3 area. In addition, Xpnpep1(−/−) CA3b pyramidal neurons were more excitable than wild-type neurons. These results indicate that insufficient astrocytic neuroprotection and enhanced neuronal excitability may underlie neurodegeneration and hippocampal dysfunction in aminopeptidase P1 deficiency. |
format | Online Article Text |
id | pubmed-7806765 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-78067652021-01-14 Altered hippocampal gene expression, glial cell population, and neuronal excitability in aminopeptidase P1 deficiency Yoon, Sang Ho Bae, Young-Soo Oh, Sung Pyo Song, Woo Seok Chang, Hanna Kim, Myoung-Hwan Sci Rep Article Inborn errors of metabolism are often associated with neurodevelopmental disorders and brain injury. A deficiency of aminopeptidase P1, a proline-specific endopeptidase encoded by the Xpnpep1 gene, causes neurological complications in both humans and mice. In addition, aminopeptidase P1-deficient mice exhibit hippocampal neurodegeneration and impaired hippocampus-dependent learning and memory. However, the molecular and cellular changes associated with hippocampal pathology in aminopeptidase P1 deficiency are unclear. We show here that a deficiency of aminopeptidase P1 modifies the glial population and neuronal excitability in the hippocampus. Microarray and real-time quantitative reverse transcription-polymerase chain reaction analyses identified 14 differentially expressed genes (Casp1, Ccnd1, Myoc, Opalin, Aldh1a2, Aspa, Spp1, Gstm6, Serpinb1a, Pdlim1, Dsp, Tnfaip6, Slc6a20a, Slc22a2) in the Xpnpep1(−/−) hippocampus. In the hippocampus, aminopeptidase P1-expression signals were mainly detected in neurons. However, deficiency of aminopeptidase P1 resulted in fewer hippocampal astrocytes and increased density of microglia in the hippocampal CA3 area. In addition, Xpnpep1(−/−) CA3b pyramidal neurons were more excitable than wild-type neurons. These results indicate that insufficient astrocytic neuroprotection and enhanced neuronal excitability may underlie neurodegeneration and hippocampal dysfunction in aminopeptidase P1 deficiency. Nature Publishing Group UK 2021-01-13 /pmc/articles/PMC7806765/ /pubmed/33441619 http://dx.doi.org/10.1038/s41598-020-79656-6 Text en © The Author(s) 2021 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 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/. |
spellingShingle | Article Yoon, Sang Ho Bae, Young-Soo Oh, Sung Pyo Song, Woo Seok Chang, Hanna Kim, Myoung-Hwan Altered hippocampal gene expression, glial cell population, and neuronal excitability in aminopeptidase P1 deficiency |
title | Altered hippocampal gene expression, glial cell population, and neuronal excitability in aminopeptidase P1 deficiency |
title_full | Altered hippocampal gene expression, glial cell population, and neuronal excitability in aminopeptidase P1 deficiency |
title_fullStr | Altered hippocampal gene expression, glial cell population, and neuronal excitability in aminopeptidase P1 deficiency |
title_full_unstemmed | Altered hippocampal gene expression, glial cell population, and neuronal excitability in aminopeptidase P1 deficiency |
title_short | Altered hippocampal gene expression, glial cell population, and neuronal excitability in aminopeptidase P1 deficiency |
title_sort | altered hippocampal gene expression, glial cell population, and neuronal excitability in aminopeptidase p1 deficiency |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806765/ https://www.ncbi.nlm.nih.gov/pubmed/33441619 http://dx.doi.org/10.1038/s41598-020-79656-6 |
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