Neuroplastin deletion in glutamatergic neurons impairs selective brain functions and calcium regulation: implication for cognitive deterioration

Abstract The cell adhesion molecule neuroplastin (Np) is a novel candidate to influence human intelligence. Np-deficient mice display complex cognitive deficits and reduced levels of Plasma Membrane Ca2+ ATPases (PMCAs), an essential regulator of the intracellular Ca2+ concentration ([iCa2+]) and ne...

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Autores principales:	Rodrigo Herrera-Molina, Kristina Mlinac-Jerkovic, Katarina Ilic, Franziska Stöber, Sampath Kumar Vemula, Mauricio Sandoval, Natasa Jovanov Milosevic, Goran Simic, Karl-Heinz Smalla, Jürgen Goldschmidt, Svjetlana Kalanj Bognar, Dirk Montag
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/242c8b715c3a4890a78cba8ca5160c63
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spelling	oai:doaj.org-article:242c8b715c3a4890a78cba8ca5160c632021-12-02T12:32:00ZNeuroplastin deletion in glutamatergic neurons impairs selective brain functions and calcium regulation: implication for cognitive deterioration10.1038/s41598-017-07839-92045-2322https://doaj.org/article/242c8b715c3a4890a78cba8ca5160c632017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07839-9https://doaj.org/toc/2045-2322Abstract The cell adhesion molecule neuroplastin (Np) is a novel candidate to influence human intelligence. Np-deficient mice display complex cognitive deficits and reduced levels of Plasma Membrane Ca2+ ATPases (PMCAs), an essential regulator of the intracellular Ca2+ concentration ([iCa2+]) and neuronal activity. We show abundant expression and conserved cellular and molecular features of Np in glutamatergic neurons in human hippocampal-cortical pathways as characterized for the rodent brain. In Nptn lox/loxEmx1Cre mice, glutamatergic neuron-selective Np ablation resulted in behavioral deficits indicating hippocampal, striatal, and sensorimotor dysfunction paralleled by highly altered activities in hippocampal CA1 area, sensorimotor cortex layers I-III/IV, and the striatal sensorimotor domain detected by single-photon emission computed tomography. Altered hippocampal and cortical activities correlated with reduction of distinct PMCA paralogs in Nptn lox/loxEmx1Cre mice and increased [iCa2+] in cultured mutant neurons. Human and rodent Np enhanced the post-transcriptional expression of and co-localized with PMCA paralogs in the plasma membrane of transfected cells. Our results indicate Np as essential for PMCA expression in glutamatergic neurons allowing proper [iCa2+] regulation and normal circuit activity. Neuron-type-specific Np ablation empowers the investigation of circuit-coded learning and memory and identification of causal mechanisms leading to cognitive deterioration.Rodrigo Herrera-MolinaKristina Mlinac-JerkovicKatarina IlicFranziska StöberSampath Kumar VemulaMauricio SandovalNatasa Jovanov MilosevicGoran SimicKarl-Heinz SmallaJürgen GoldschmidtSvjetlana Kalanj BognarDirk MontagNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rodrigo Herrera-Molina Kristina Mlinac-Jerkovic Katarina Ilic Franziska Stöber Sampath Kumar Vemula Mauricio Sandoval Natasa Jovanov Milosevic Goran Simic Karl-Heinz Smalla Jürgen Goldschmidt Svjetlana Kalanj Bognar Dirk Montag Neuroplastin deletion in glutamatergic neurons impairs selective brain functions and calcium regulation: implication for cognitive deterioration
description	Abstract The cell adhesion molecule neuroplastin (Np) is a novel candidate to influence human intelligence. Np-deficient mice display complex cognitive deficits and reduced levels of Plasma Membrane Ca2+ ATPases (PMCAs), an essential regulator of the intracellular Ca2+ concentration ([iCa2+]) and neuronal activity. We show abundant expression and conserved cellular and molecular features of Np in glutamatergic neurons in human hippocampal-cortical pathways as characterized for the rodent brain. In Nptn lox/loxEmx1Cre mice, glutamatergic neuron-selective Np ablation resulted in behavioral deficits indicating hippocampal, striatal, and sensorimotor dysfunction paralleled by highly altered activities in hippocampal CA1 area, sensorimotor cortex layers I-III/IV, and the striatal sensorimotor domain detected by single-photon emission computed tomography. Altered hippocampal and cortical activities correlated with reduction of distinct PMCA paralogs in Nptn lox/loxEmx1Cre mice and increased [iCa2+] in cultured mutant neurons. Human and rodent Np enhanced the post-transcriptional expression of and co-localized with PMCA paralogs in the plasma membrane of transfected cells. Our results indicate Np as essential for PMCA expression in glutamatergic neurons allowing proper [iCa2+] regulation and normal circuit activity. Neuron-type-specific Np ablation empowers the investigation of circuit-coded learning and memory and identification of causal mechanisms leading to cognitive deterioration.
format	article
author	Rodrigo Herrera-Molina Kristina Mlinac-Jerkovic Katarina Ilic Franziska Stöber Sampath Kumar Vemula Mauricio Sandoval Natasa Jovanov Milosevic Goran Simic Karl-Heinz Smalla Jürgen Goldschmidt Svjetlana Kalanj Bognar Dirk Montag
author_facet	Rodrigo Herrera-Molina Kristina Mlinac-Jerkovic Katarina Ilic Franziska Stöber Sampath Kumar Vemula Mauricio Sandoval Natasa Jovanov Milosevic Goran Simic Karl-Heinz Smalla Jürgen Goldschmidt Svjetlana Kalanj Bognar Dirk Montag
author_sort	Rodrigo Herrera-Molina
title	Neuroplastin deletion in glutamatergic neurons impairs selective brain functions and calcium regulation: implication for cognitive deterioration
title_short	Neuroplastin deletion in glutamatergic neurons impairs selective brain functions and calcium regulation: implication for cognitive deterioration
title_full	Neuroplastin deletion in glutamatergic neurons impairs selective brain functions and calcium regulation: implication for cognitive deterioration
title_fullStr	Neuroplastin deletion in glutamatergic neurons impairs selective brain functions and calcium regulation: implication for cognitive deterioration
title_full_unstemmed	Neuroplastin deletion in glutamatergic neurons impairs selective brain functions and calcium regulation: implication for cognitive deterioration
title_sort	neuroplastin deletion in glutamatergic neurons impairs selective brain functions and calcium regulation: implication for cognitive deterioration
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/242c8b715c3a4890a78cba8ca5160c63
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Neuroplastin deletion in glutamatergic neurons impairs selective brain functions and calcium regulation: implication for cognitive deterioration

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