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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...

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Autores principales: Yoon, Sang Ho, Bae, Young-Soo, Oh, Sung Pyo, Song, Woo Seok, Chang, Hanna, Kim, Myoung-Hwan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
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.
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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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