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

Autor:	Herrera-Molina, Rodrigo, Mlinac-Jerkovic, Kristina, Ilic, Katarina, Stöber, Franziska, Vemula, Sampath Kumar, Sandoval, Mauricio, Milosevic, Natasa Jovanov, Simic, Goran, Smalla, Karl-Heinz, Goldschmidt, Jürgen, Bognar, Svjetlana Kalanj, Montag, Dirk
Jazyk:	angličtina
Rok vydání:	2017
Předmět:	Aged 80 and over Mice Knockout Neurons Membrane Glycoproteins Science Brain Gene Expression Middle Aged Article Mice Protein Transport Cerebrovascular Circulation neuroplastin PMCA cognition mechanisms glutamatergic neurons calcium homeostasis learning impairment memory deficits synaptopathy Animals Humans Medicine Calcium Molecular neuroscience Spatial memory Cognition Disorders Biomarkers Aged
Zdroj:	Scientific Reports, Vol 7, Iss 1, Pp 1-13 (2017) Scientific reports, 7:7273 Scientific Reports
ISSN:	2045-2322
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=pmid_dedup__::1a9092c2dc9e19c634b6d101aa8d3967 https://doaj.org/article/242c8b715c3a4890a78cba8ca5160c63 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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