Anti-CAMK2G (full length) polyclonal antibody

Objectives: Venlafaxine (VLX), a serotonine-noradrenaline reuptake inhibitor, is one of the most commonly used antidepressant drugs in clinical practice for the treatment of major depressive disorder (MDD). Despite being more potent than its predecessors, similarly to them, the therapeutical effect of VLX is visible only 3-4 weeks after the beginning of treatment. Furthermore, recent papers show that antidepressants, including also VLX, enhance the motor recovery after stroke even in non depressed persons. In the present, transcriptomic-based study we looked for changes in gene expressions after a long-term VLX administration. Methods: Osmotic minipumps were implanted subcutaneously into Dark Agouti rats providing a continuous (40 mg/kg/day) VLX delivery for three weeks. Frontal regions of the cerebral cortex were isolated and analyzed using Illumina bead arrays to detect genes showing significant chances in expression. Gene set enrichment analysis was performed to identify specific regulatory networks significantly affected by long term VLX treatment. Results: Chronic VLX administration may have an effect on neurotransmitter release via the regulation of genes involved in vesicular exocytosis and receptor endocytosis (such as Kif proteins, Myo5a, Sv2b, Syn2 or Synj2). Simultaneously, VLX activated the expression of genes involved in neurotrophic signaling (Ntrk2, Ntrk3), glutamatergic transmission (Gria3, Grin2b and Grin2a), neuroplasticity (Camk2g/b, Cd47), synaptogenesis (Epha5a, Gad2) and cognitive processes (Clstn2). Interestingly, VLX increased the expression of genes involved in mitochondrial antioxidant activity (Bcl2 and Prdx1). Additionally, VLX administration also modulated genes related to insulin signaling pathway (Negr1, Ppp3r1, Slc2a4 and Enpp1), a mechanism that has recently been linked to neuroprotection, learning and memory. Conclusions: Our results strongly suggest that chronic VLX treatment improves functional reorganization and brain plasticity by influencing gene expression in regulatory networks of motor cortical areas. These results are consonant with the synaptic (network) hypothesis of depression and antidepressant-induced motor recovery after stroke.

Disturbances in glutamate signaling caused by disruption of N-methyl-D-aspartate-type glutamate receptor (NMDAR) have been implicated in schizophrenia. Findings suggested that miR-219, miR-132 and miR-107 could involve in NMDAR signaling by influencing the expression of pathway genes or the signaling transmission and single nucleotide polymorphisms (SNPs) within miRNA genes or miRNA target sites could result in their functional changes. Therefore, we hypothesized that SNPs in miRNAs and/or their target sites were associated with schizophrenia. 3 SNPs in hsa-pri-miR- 219/132/107 and 6 SNPs in 3' UTRs of GRIN2A/2B/3A and CAMK2G were selected and genotyped in a case-control study of 1041 schizophrenia cases and 953 healthy controls in Chinese Han population. In the present study, GRIN2B rs890 showed significant associations with schizophrenia. Further functional analyses showed that the rs890 variant C allele led to significantly lower luciferase activity, compared with the A allele. MDR analysis showed that a 4-locus model including rs107822, rs2306327, rs890 and rs12342026 was the best model. These findings suggest that GRIN2B may be associated with schizophrenia and interaction effects of the polymorphisms in hsa-miR-219, CAKM2G, GRIN2B and GRIN3A may confer susceptibility to schizophrenia in the Chinese Han population.