Altered hippocampal gene expression, glial cell population, and neuronal excitability in aminopeptidase P1 deficiency

Abstract 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-def...

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Autores principales:	Sang Ho Yoon, Young-Soo Bae, Sung Pyo Oh, Woo Seok Song, Hanna Chang, Myoung-Hwan Kim
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/97a9a9fc35484ae295a4e9f21a1be55a
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spelling	oai:doaj.org-article:97a9a9fc35484ae295a4e9f21a1be55a2021-12-02T15:23:04ZAltered hippocampal gene expression, glial cell population, and neuronal excitability in aminopeptidase P1 deficiency10.1038/s41598-020-79656-62045-2322https://doaj.org/article/97a9a9fc35484ae295a4e9f21a1be55a2021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-79656-6https://doaj.org/toc/2045-2322Abstract 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.Sang Ho YoonYoung-Soo BaeSung Pyo OhWoo Seok SongHanna ChangMyoung-Hwan KimNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-17 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sang Ho Yoon Young-Soo Bae Sung Pyo Oh Woo Seok Song Hanna Chang Myoung-Hwan Kim Altered hippocampal gene expression, glial cell population, and neuronal excitability in aminopeptidase P1 deficiency
description	Abstract 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	article
author	Sang Ho Yoon Young-Soo Bae Sung Pyo Oh Woo Seok Song Hanna Chang Myoung-Hwan Kim
author_facet	Sang Ho Yoon Young-Soo Bae Sung Pyo Oh Woo Seok Song Hanna Chang Myoung-Hwan Kim
author_sort	Sang Ho Yoon
title	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_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_sort	altered hippocampal gene expression, glial cell population, and neuronal excitability in aminopeptidase p1 deficiency
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/97a9a9fc35484ae295a4e9f21a1be55a
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Altered hippocampal gene expression, glial cell population, and neuronal excitability in aminopeptidase P1 deficiency

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