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

Montag, Dirk; Milosevic, Natasa Jovanov; Herrera-Molina, Rodrigo; Simic, Goran; Ilic, Katarina; Smalla, Karl-Heinz; Vemula, Sampath Kumar; Goldschmidt, Juergen; Mlinac-Jerkovic, Kristina; Bognar, Svjetlana Kalanj; Sandoval, Mauricio; Stoeber, Franziska

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 ([iCa(2+)]) 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 [iCa(2+)] 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 [iCa(2+)] 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.

Más información

Título según WOS: ID WOS:000406980800012 Not found in local WOS DB
Título de la Revista: SCIENTIFIC REPORTS
Volumen: 7
Editorial: Nature Research
Fecha de publicación: 2017
DOI:

10.1038/s41598-017-07839-9

Notas: ISI