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

Herrera-Molina, Rodrigo and Mlinac-Jerković, Kristina and Ilić, Katarina and Stöber, Franziska and Vemula, Sampath Kumar and Sandoval, Mauricio and Jovanov Milošević, Nataša and Šimić, Goran and Smalla, Karl-Heinz and Goldschmidt, Jürgen and Kalanj Bognar, Svjetlana and Montag, Dirk (2017) Neuroplastin deletion in glutamatergic neurons impairs selective brain functions and calcium regulation: implication for cognitive deterioration. Scientific Reports, 7 (1). p. 7273. ISSN 2045-2322

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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.

Item Type: Article
Additional Information: 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 license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license 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 license, visit http://creativecommons.org/licenses/by/4.0/. © The Author(s) 2017
Departments: Hrvatski institut za istraživanje mozga
Katedra za medicinsku biologiju
Katedra za medicinsku kemiju, biokemiju i kliničku kemiju
Katedra za neurologiju
Depositing User: Martina Žužak
Status: Published
Creators:
CreatorsEmail
Herrera-Molina, RodrigoUNSPECIFIED
Mlinac-Jerković, KristinaUNSPECIFIED
Ilić, KatarinaUNSPECIFIED
Stöber, FranziskaUNSPECIFIED
Vemula, Sampath KumarUNSPECIFIED
Sandoval, MauricioUNSPECIFIED
Jovanov Milošević, NatašaUNSPECIFIED
Šimić, GoranUNSPECIFIED
Smalla, Karl-HeinzUNSPECIFIED
Goldschmidt, JürgenUNSPECIFIED
Kalanj Bognar, SvjetlanaUNSPECIFIED
Montag, DirkUNSPECIFIED
Date: 4 August 2017
Date Deposited: 02 Mar 2018 10:54
Last Modified: 02 Mar 2018 10:54
Subjects: UNSPECIFIED
Related URLs:
URI: http://medlib.mef.hr/id/eprint/2838

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