Neuroplastin deletion in glutamatergic neurons impairs selective brain functions and calcium regulation: implication for cognitive deterioration.
Neuroplastin deletion in glutamatergic neurons impairs selective brain functions and calcium regulation: implication for cognitive deterioration.
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DOI：
10.1038/s41598-017-07839-9
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发表时间：
2017-08-04
影响因子：
4.6
通讯作者：
Montag D
中科院分区：
文献类型：
--
作者：
Herrera-Molina R;Mlinac-Jerkovic K;Ilic K;Stöber F;Vemula SK;Sandoval M;Milosevic NJ;Simic G;Smalla KH;Goldschmidt J;Bognar SK;Montag D
细胞粘附分子神经活素（Np）是影响人类智力的新候选分子。np缺陷小鼠表现出复杂的认知缺陷和质膜Ca2+ atp酶（PMCAs）水平降低，PMCAs是细胞内Ca2+浓度（[iCa2+]）和神经元活动的重要调节剂。我们发现Np在人类海马-皮质通路谷氨酸能神经元中的丰富表达和保守的细胞和分子特征与啮齿动物大脑的特征相同。在Nptn lox/loxEmx1Cre小鼠中，谷氨酸能神经元选择性Np切除导致行为缺陷，表明海马、纹状体和感觉运动功能障碍，并与海马CA1区、感觉运动皮层I-III/IV层和纹状体感觉运动区域的活动高度改变并行。在Nptn lox/loxEmx1Cre小鼠中，海马和皮质活动的改变与不同PMCA相似物的减少相关，并在培养的突变神经元中增加[iCa2+]。人和啮齿类动物的Np增强了转染细胞质膜中PMCA类似物的转录后表达和共定位。我们的研究结果表明，Np对于谷氨酸能神经元中PMCA的表达至关重要，允许适当的[iCa2+]调节和正常的回路活动。神经元类型特异性Np消融增强了对电路编码学习和记忆的研究，并确定了导致认知退化的因果机制。
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.
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影响因子：
10.6
作者：
Carayol, Jerome;Sacco, Roberto;Persico, Antonio M.
通讯作者：
Persico, Antonio M.
影响因子：
2.5
作者：
Burette, Alain C.;Strehler, Emanuel E.;Weinberg, Richard J.
通讯作者：
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影响因子：
4.8
作者：
Langnaese, K;Beesley, PW;Gundelfinger, ED
通讯作者：
Gundelfinger, ED
影响因子：
5.7
作者：
Kolodziej, Angela;Lippert, Michael;Goldschmidt, Juergen
通讯作者：
Goldschmidt, Juergen
影响因子：
4.8
作者：
Herrera-Molina, Rodrigo;Sarto-Jackson, Isabella;Montag, Dirk
通讯作者：
Montag, Dirk