The molecular interaction between the glutamatergic, noradrenergic, dopaminergic and serotoninergic systems informs a detailed genetic perspective on depressive phenotypes |
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| Authors: | Drago Antonio Crisafulli Concetta Sidoti Antonina Serretti Alessandro |
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| Affiliation: | Institute of Psychiatry, University of Bologna, Viale Carlo Pepoli 5, 40123 Bologna, Italy. |
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| Abstract: | The glutamatergic pathway has been consistently involved in the physiopathology of depressive disorder. However a complete dissection and integration of its role in the context of other known mechanisms is lacking. We summarized and integrated the evidence of various levels of interaction between glutamatergic and monoaminergic pathways (see videos). We identified six molecular pathways, some of which with specific regional distribution within the brain. From the six pathways we identified the key proteins and their coding genes, we then provided a detailed list of possible candidates with practical suggestions for association studies planning. |
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| Keywords: | 5-HT, serotonin 5-HT1A, 5-HT receptor 1A 5-HT1B, 5-HT receptor 1B 5-HT2A, 5-HT receptor 2A 5-HT6, 5-HT receptor 6 ABP, AMPAR-binding protein AIF, apoptosis-inducing factor AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazole propionate Arc, cytoskeletal-associated protein CaM, calmodulin CaMKII, Ca2+/calmodulin-dependent protein kinases or CaM kinases CREB, cAMP response element binding protein DA D1, dopamine receptor D1 DA D2, dopamine receptor D2 DA D4, dopamine receptor D4 DA, dopamine DAG, diacylglycerol DISC1, disrupted-in-schizophrenia 1 EAAT, excitatory amino acid transporters ERK, extracellular signal regulated kinases GABA, gamma-aminobutyric acid GPCRs, G protein-coupled receptors GRIP, glutamate receptor interacting protein GWAS, genome wide analyses studies IDO, indoleamine 2,3-dioxygenase iGluRs, ionotropic glutamate receptors KA, kainate LTDP, long term depotentiation LTP, long term potentiation MAP kinase, mitogene activated protein kinase MDD, major depressive disorder mGluRs, metabotropic glutamate receptors NE, norepinephrine NFL, neurofilaments NMDA, N-methyl-d-aspartate nNOS, nitric oxide synthase NSF, N-ethylmaleimide-sensitive fusion protein PAG, phosphate activated glutaminase PARS, poly(ADP-ribose) synthase PDE, phosphodiesterase PI, polyphosphoinositide PICK1, protein interacting with C alpha kinase 1 PKA, protein kinase A PKC, protein kinase C PLC, phospholipase C PLC, phospholipase C PP1, protein phosphatase 1 PSD-95, postsynaptic density 95 SAP97, synapse-associated protein 97 SERT, serotonin transporter sGC, soluble guanylate cyclase SNARE, soluble N-ethylmaleimide-sensitive factor attachment receptor SYN, synaptophysin TCA, tricarboxylic acid cycle VGLUT, vesicular glutamate transporters CNS, central nervous system |
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