Anti-NRGN monoclonal antibody Made to order

Extracellular vesicles (EVs) are cell-derived structures that transport proteins, lipids and nucleic acids between cells, thereby affecting the phenotype of the recipient cell. As the content of EVs reflects the status of the originating cell, EVs can have potential as biomarkers. Identifying EVs, including their cells of origin and their cargo, may provide insights in the pathophysiology of psychosis. Here, we present an in-depth analysis and proteomics of EVs from peripheral blood in patients (n = 25) during and after the acute phase of psychosis. Concentration and protein content of EVs in psychotic patients were twofold higher than in 25 age- and sex-matched healthy controls (p < 0.001 for both concentration and protein content), and the diameter of EVs was larger in patients (p = 0.02). Properties of EVs did not differ significantly in blood sampled during and after the acute psychotic episode. Proteomic analyses on isolated EVs from individual patients revealed 1,853 proteins, whereof 45 were brain-elevated proteins. Of these, five proteins involved in regulation of plasticity of glutamatergic synapses were significantly different in psychotic patients compared to controls; neurogranin (NRGN), neuronspecific calcium-binding protein hippocalcin (HPCA), kalirin (KALRN), beta-adducin (ADD2) and ankyrin-2 (ANK2). To summarize, our results show that peripheral EVs in psychotic patients are different from those in healthy controls and point at alterations on the glutamatergic system. We suggest that EVs allow investigation of blood-borne brain-originating biological material and that their role as biomarkers in patients with psychotic disorders is worthy of further exploration.

A replicative analysis of associations of 15 SNPs located in the regions of 11 genes (TCF4, VRK2, NOTCH4, ZNF804A, AGBL1, RELN, ZFP64P1, KCNB2, CSMD1, CPVL, NRIP1) and three intergenic regions (SLCO6A1/LINCOO491, LOC105376248/LOC105376249, SPA17/NRGN) with schizophrenia was conducted in the Russian population of the Siberian region. These SNPs were previously identified in genome-wide association studies (GWAS) of schizophrenia and cognitive abnormalities. The present study confirmed associations of KCNB2 rs2247572, CSMD1 rs2616984, and intergenic rs12807809 located in SPA17/NRGN with schizophrenia. It was established that the frequency of the CSMD1 rs2616984 G/G genotype was higher in patients compared to the control group (OR = 1.73; CI: 1.14-2.62; NEuro = 0.0337). The frequencies of the KCNB2 rs2247572 TT genotype (OR = 0.41; CI: 0.20-0.87; NEuro = 0.0485) and intergenic rs12807809 CT genotype located in SPA17/NRGN (OR = 0.70; CI: 0.53-0.94; NEuro = 0.0464) were significantly decreased in patients compared to the control group.