|1||Neurosci. Lett. 2007 Jan 411: 168-73|
|Title||Association study of putative promoter polymorphisms in the neuroplastin gene and schizophrenia.|
|Abstract||A previous study revealed a number of methamphetamine (METH) and phencyclidine (PCP)-reactive tags in a rat brain through serial analysis of gene expression. The present study extends this previous study by investigating whether two genes, which deduced from METH/PCP-reactive tags, were identified as those encoding human transmembrane proteins of the immunoglobulin (Ig) superfamily, neuroplastin (NPTN) and basigin (BSG), confer genetic susceptibility to schizophrenia by analyzing single nucleotide polymorphisms (SNPs). There were nominally significant differences between the two groups in their allelic frequencies (T Ins/Del, chi2=4.910, d.f.=1, P=0.040) and genotypic distributions (T/T or T/Del, chi2=5.116, d.f.=1, P=0.036) of rs3840846 in the 5'-upstream of NPTN. The two groups differed significantly also in their allelic frequencies (G/T, chi2=4.229, d.f.=1, P=0.044), but not genotypic distributions of rs3743500 in the 5'-upstream of NPTN. The haplotypes constructed from the three SNPs (rs3840846, rs3826047 and rs3743500, in order) in the 5'-upstream of NPTN showed a significant association with schizophrenia (permutation P=0.036), in that T-G-T (permutation P=0.028) and del-G-G (permutation P=0.040) were under-represented and over-represented, respectively, in schizophrenia. A reporter construct driven by the 5'-upstream region containing any haplotype consisting of the three SNPs had substantial transcriptional activity. Notably, a reporter construct containing a haplotype T-G-T had significantly lower transcriptional activity as compared with one having a haplotype T-G-G or T-A-G. There was no significant difference between the two groups regarding allelic frequencies, genotypic distribution or the adopted SNP-combinatory haplotype for BSG. These results suggest that NPTN may be involved in genetic susceptibility to schizophrenia.|
|2||J. Neurochem. 2014 Nov 131: 268-83|
|Title||The Neuroplastin adhesion molecules: key regulators of neuronal plasticity and synaptic function.|
|Abstract||The Neuroplastins Np65 and Np55 are neuronal and synapse-enriched immunoglobulin superfamily molecules that play important roles in a number of key neuronal and synaptic functions including, for Np65, cell adhesion. In this review we focus on the physiological roles of the Neuroplastins in promoting neurite outgrowth, regulating the structure and function of both inhibitory and excitatory synapses in brain, and in neuronal and synaptic plasticity. We discuss the underlying molecular and cellular mechanisms by which the Neuroplastins exert their physiological effects and how these are dependent upon the structural features of Np65 and Np55, which enable them to bind to a diverse range of protein partners. In turn this enables the Neuroplastins to interact with a number of key neuronal signalling cascades. These include: binding to and activation of the fibroblast growth factor receptor; Np65 trans-homophilic binding leading to activation of p38 MAPK and internalization of glutamate (GluR1) receptor subunits; acting as accessory proteins for monocarboxylate transporters, thus affecting neuronal energy supply, and binding to GABAA ?1, 2 and 5 subunits, thus regulating the composition and localization of GABAA receptors. An emerging theme is the role of the Neuroplastins in regulating the trafficking and subcellular localization of specific binding partners. We also discuss the involvement of Neuroplastins in a number of pathophysiological conditions, including ischaemia, schizophrenia and breast cancer and the role of a single nucleotide polymorphism in the human Neuroplastin (NPTN) gene locus in impairment of cortical development and cognitive functions. Neuroplastins are neuronal cell adhesion molecules, which induce neurite outgrowth and play important roles in synaptic maturation and plasticity. This review summarizes the functional implications of Neuroplastins for correct synaptic membrane protein localization, neuronal energy supply, expression of LTP and LTD, animal and human behaviour, and pathophysiology and disease. It focuses particularly on Neuroplastin binding partners and signalling mechanisms, and proposes perspectives for future research on these important immunoglobulin superfamily members.|
|3||Biol. Psychiatry 2016 Apr -1: -1|
|Title||Genetically Induced Retrograde Amnesia of Associative Memories After Neuroplastin Ablation.|
|Abstract||Neuroplastin cell recognition molecules have been implicated in synaptic plasticity. Polymorphisms in the regulatory region of the human neuroplastin gene (NPTN) are correlated with cortical thickness and intellectual abilities in adolescents and in individuals with schizophrenia.|
We characterized behavioral and functional changes in inducible conditional neuroplastin-deficient mice.
We demonstrate that neuroplastins are required for associative learning in conditioning paradigms, e.g., two-way active avoidance and fear conditioning. Retrograde amnesia of learned associative memories is elicited by inducible neuron-specific ablation of NPTN gene expression in adult mice, which shows that neuroplastins are indispensable for the availability of previously acquired associative memories. Using single-photon emission computed tomography imaging in awake mice, we identified brain structures activated during memory recall. Constitutive neuroplastin deficiency or NPTN gene ablation in adult mice causes substantial electrophysiologic deficits such as reduced long-term potentiation. In addition, neuroplastin-deficient mice reveal profound physiologic and behavioral deficits, some of which are related to depression and schizophrenia, which illustrate neuroplastin's essential functions.
Neuroplastins are essential for learning and memory. Retrograde amnesia after an associative learning task can be induced by ablation of the neuroplastin gene. The inducible neuroplastin-deficient mouse model provides a new and unique means to analyze the molecular and cellular mechanisms underlying retrograde amnesia and memory.