For the current study, published in Psychiatric Genetics, the DNA sequences of over 4,000 people with schizophrenia and 5,000 controls were used to study variants in the three genes which code for NMDAR (GRIN1
, GRIN2A and GRIN2B) and a fourth (FYN), for a protein called Fyn which controls NMDAR functioning.
N-Methyl-D-aspartate receptors (NMDA) receptors are tetrameric structures (8), consist of Grin1
, Grin2 (A-D) and Grin3 (A-B) subunits (9), and mediates postsynaptic [Ca.sup.2+] influx in dendritic spines (3).
Furthermore, both the gain- and loss-of-function phenotype can be observed in other channelopathies such as KCNA2, GRIN1
, and DEAF1 gene mutations.
We compared our dataset with a curated list of a total 601 genes and molecules implicated in psychological depression (IPA) and found 13 genes common showing significant differential methylation (Figure 2, Supplement 4), including BTG2, FABP6, GRIN1
, HRH1, HSD17B1, MDFI, OXT, and TSPO.
Few changes in overall transcript expression were observed in these mice, but there were substantial changes in the relative abundance of particular transcripts, including genes involved in membrane excitability (Gabrg2, Grin1
, Scn8a, and Snap25), but also the CAMs Nrcam and Nrxn3.
, which encodes the essential glutamate (NMDA) receptor subunit C-1 (Monyer et al., 1992), was increased at very early stages of differentiation (one week after induction of differentiation) and continued to increase up to 5 weeks (Fig.
reported epigenetic alterations in DNA derived from saliva in three genes predicted depression in a cohort of maltreated children: ID3, Glutamate NMDA Receptor (GRIN1
), and Tubulin Polymerization Promoting Protein (TPPP) .
Disease or Function p-Value Molecules # Mole Annotation cules Mood disorders 3.73E--04 ADRA2B, ALOX12, AQP4, CA9, 22 CACNB2, CCKBR, CHRNA1, CHR NB4, CHRNG, DDC, ESR1, GRIA3, GRIK2, GRIN1
, KCNK2, MTNR 1A, MYOM1, NCAM1, NDUFS7, PDE11A, SCN11A, SCN2B Depressive disorder 7.90E--04 ADRA2B, AQP4, CACNB2, 14 CCKBR, CHRNA1, CHRNB4, CHRNG, ESR1, GRIA3, GRIN1
, KCNK2, MYOM1, NCAM1, PDE11A Table 3 Effect of Rhodiola on genes involved in depression ([section]).
They found that expression levels of the NMDA receptor genes GRIN1
, GRIN2A, and GRIN2D increased following cell cultures exposed to alcohol for 7 days.
Treatment, gene Fold change Dex PRR16 11.71 GMPR 10.39 PNMT 9.46 TDRD9 8.84 PER1 8.60 FRMD4A -9.23 TMEM191B -15.05 NEUROG1 -16.06 ELF5 -19.49 ZNF775 -25.45 Gen CACNA1I 20.67 MSMB 19.54 NPPC 9.39 ALPPL2 9.24 CA12 8.95 FOXB1 -23.44 ATN1 -28.07 SYNPO -35.99 GRIN1
-37.20 ZNF775 -40.56 Dex + Gen MSMB 30.26 MICALCL 16.38 CACNA1I 15.48 CAMP 12.98 DHRS3 11.49 SP5 -17.21 NEUROG1 -17.68 TMEM191B -18.02 ELF5 -39.80 ZNF775 -45.33
Previa extraccion del ADN genomico de 200 [micron]l de sangre completa, con el kit Qiagen DNA Minikit (QIAGEN), se determinaron mediante reaccion en cadena de la polimerasa (PCR) en tiempo real los SNP seleccionados de los genes ABCB1 (rs1045642), CYP2B6 (rs3745274), OPRM1 (rs1799971), ARRB2 (rs3786047, rs2036657 y rs1045280), DfiH (rs1611115), GRIN1
(rs6293, rs4880215 y rs2301364) y POR (rs1057868, rs28931608 y rs28931608).