Organelle and cellular abnormalities associated with hippocampal heterotopia in neonatal doublecortin knockout mice.

Heterotopic or aberrantly positioned cortical neurons are associated with epilepsy and intellectual disability. Various mouse models exist with forms of heterotopia, but the composition and state of cells developing in heterotopic bands has been little studied. Dcx knockout (KO) mice show hippocampa...

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Autores principales:	Reham Khalaf-Nazzal, Elodie Bruel-Jungerman, Jean-Paul Rio, Jocelyne Bureau, Theano Irinopoulou, Iffat Sumia, Audrey Roumegous, Elodie Martin, Robert Olaso, Carlos Parras, Carmen Cifuentes-Diaz, Fiona Francis
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5f58f254f6e24b13a0403da23f1b4ca0
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spelling	oai:doaj.org-article:5f58f254f6e24b13a0403da23f1b4ca02021-11-18T08:57:25ZOrganelle and cellular abnormalities associated with hippocampal heterotopia in neonatal doublecortin knockout mice.1932-620310.1371/journal.pone.0072622https://doaj.org/article/5f58f254f6e24b13a0403da23f1b4ca02013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24023755/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Heterotopic or aberrantly positioned cortical neurons are associated with epilepsy and intellectual disability. Various mouse models exist with forms of heterotopia, but the composition and state of cells developing in heterotopic bands has been little studied. Dcx knockout (KO) mice show hippocampal CA3 pyramidal cell lamination abnormalities, appearing from the age of E17.5, and mice suffer from spontaneous epilepsy. The Dcx KO CA3 region is organized in two distinct pyramidal cell layers, resembling a heterotopic situation, and exhibits hyperexcitability. Here, we characterized the abnormally organized cells in postnatal mouse brains. Electron microscopy confirmed that the Dcx KO CA3 layers at postnatal day (P) 0 are distinct and separated by an intermediate layer devoid of neuronal somata. We found that organization and cytoplasm content of pyramidal neurons in each layer were altered compared to wild type (WT) cells. Less regular nuclei and differences in mitochondria and Golgi apparatuses were identified. Each Dcx KO CA3 layer at P0 contained pyramidal neurons but also other closely apposed cells, displaying different morphologies. Quantitative PCR and immunodetections revealed increased numbers of oligodendrocyte precursor cells (OPCs) and interneurons in close proximity to Dcx KO pyramidal cells. Immunohistochemistry experiments also showed that caspase-3 dependent cell death was increased in the CA1 and CA3 regions of Dcx KO hippocampi at P2. Thus, unsuspected ultrastructural abnormalities and cellular heterogeneity may lead to abnormal neuronal function and survival in this model, which together may contribute to the development of hyperexcitability.Reham Khalaf-NazzalElodie Bruel-JungermanJean-Paul RioJocelyne BureauTheano IrinopoulouIffat SumiaAudrey RoumegousElodie MartinRobert OlasoCarlos ParrasCarmen Cifuentes-DiazFiona FrancisPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 9, p e72622 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Reham Khalaf-Nazzal Elodie Bruel-Jungerman Jean-Paul Rio Jocelyne Bureau Theano Irinopoulou Iffat Sumia Audrey Roumegous Elodie Martin Robert Olaso Carlos Parras Carmen Cifuentes-Diaz Fiona Francis Organelle and cellular abnormalities associated with hippocampal heterotopia in neonatal doublecortin knockout mice.
description	Heterotopic or aberrantly positioned cortical neurons are associated with epilepsy and intellectual disability. Various mouse models exist with forms of heterotopia, but the composition and state of cells developing in heterotopic bands has been little studied. Dcx knockout (KO) mice show hippocampal CA3 pyramidal cell lamination abnormalities, appearing from the age of E17.5, and mice suffer from spontaneous epilepsy. The Dcx KO CA3 region is organized in two distinct pyramidal cell layers, resembling a heterotopic situation, and exhibits hyperexcitability. Here, we characterized the abnormally organized cells in postnatal mouse brains. Electron microscopy confirmed that the Dcx KO CA3 layers at postnatal day (P) 0 are distinct and separated by an intermediate layer devoid of neuronal somata. We found that organization and cytoplasm content of pyramidal neurons in each layer were altered compared to wild type (WT) cells. Less regular nuclei and differences in mitochondria and Golgi apparatuses were identified. Each Dcx KO CA3 layer at P0 contained pyramidal neurons but also other closely apposed cells, displaying different morphologies. Quantitative PCR and immunodetections revealed increased numbers of oligodendrocyte precursor cells (OPCs) and interneurons in close proximity to Dcx KO pyramidal cells. Immunohistochemistry experiments also showed that caspase-3 dependent cell death was increased in the CA1 and CA3 regions of Dcx KO hippocampi at P2. Thus, unsuspected ultrastructural abnormalities and cellular heterogeneity may lead to abnormal neuronal function and survival in this model, which together may contribute to the development of hyperexcitability.
format	article
author	Reham Khalaf-Nazzal Elodie Bruel-Jungerman Jean-Paul Rio Jocelyne Bureau Theano Irinopoulou Iffat Sumia Audrey Roumegous Elodie Martin Robert Olaso Carlos Parras Carmen Cifuentes-Diaz Fiona Francis
author_facet	Reham Khalaf-Nazzal Elodie Bruel-Jungerman Jean-Paul Rio Jocelyne Bureau Theano Irinopoulou Iffat Sumia Audrey Roumegous Elodie Martin Robert Olaso Carlos Parras Carmen Cifuentes-Diaz Fiona Francis
author_sort	Reham Khalaf-Nazzal
title	Organelle and cellular abnormalities associated with hippocampal heterotopia in neonatal doublecortin knockout mice.
title_short	Organelle and cellular abnormalities associated with hippocampal heterotopia in neonatal doublecortin knockout mice.
title_full	Organelle and cellular abnormalities associated with hippocampal heterotopia in neonatal doublecortin knockout mice.
title_fullStr	Organelle and cellular abnormalities associated with hippocampal heterotopia in neonatal doublecortin knockout mice.
title_full_unstemmed	Organelle and cellular abnormalities associated with hippocampal heterotopia in neonatal doublecortin knockout mice.
title_sort	organelle and cellular abnormalities associated with hippocampal heterotopia in neonatal doublecortin knockout mice.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/5f58f254f6e24b13a0403da23f1b4ca0
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Organelle and cellular abnormalities associated with hippocampal heterotopia in neonatal doublecortin knockout mice.

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