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

Autori
Herrera-Molina, Rodrigo ; Mlinac Jerković, Kristina ; Ilić, Katarina ; Stöber, Franziska ; Vemula, Sampath Kumar ; Sandoval, Mauricio ; Jovanov Milošević, Nataša ; Šimić, Goran ; Smalla, Karl-Heinz ; Goldschmidt, Jürgen ; Kalanj Bognar, Svjetlana ; Montag, Dirk

Izvornik
Scientific Reports (2045-2322) 7 (2017), 1; 7273-1

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
neuroplastin ; PMCA ; cognition mechanisms ; glutamatergic neurons, calcium homeostasis ; learning impairment ; memory deficits ; synaptopathy

Sažetak
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 Nptnlox/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 Nptnlox/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.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA