KEGG pathway analysis identified 2 enriched pathways, hsa04080: Neuroactive ligand-receptor interaction (GRM8, DRD5, GRIN3A, FSHR) and hsa04024: cAMP signaling pathway (DRD5, GRIN3A, FSHR) (Table 4).
The genes APP, SGSM1, ROR1, PDGFRB, GRIN3A, SEZ6L, NCOR1, FSHR, SLC22A2, TBC1D32, OCA2, and ASAH1, which also encompassed nsSNPs, were classified into Alzheimer's disease after reference to the GAD.
Grin3A has multiple role in synaptic development in early postnatal stages, participate in neuron-glia interaction and regulation of myelin formation (8).
CalbindinD28k, NM_031984.1, UPL Probe #128 (Roche 04693647001); Parvalbumin, NM_022499.1, UPL Probe #49 (Roche 04688104001); Grin1 NM_001270602.1 UPL Probe #69 (Roche 04688686001); Grin2a NM_012573.3 UPL Probe #66 (Roche 04688651001); Grin2b NM_012574.1 UPL Probe # 29 (Roche 04687612001); Grin2c NM_012575.3 UPL Probe #106 (Roche 04692250001); Grin2d NM_022797.1 UPL Probe #4 (Roche 04685016001); Grin3a NM_001198583.1 UPL Probe #105 (Roche 04692241001) CACNA1C, NM_012517.2, UPL Probe #73 (Roche 04688961001); CACNA1D, NM_017298.1, UPL Probe #82 (Roche 04689054001).
On the other hand, Grin2 d and Grin3a mRNA levels did not change after 4 hours of treatment.
It was demonstrated that the mRNAs present in EVs are associated with the mesenchymal phenotype and with several cell functions related to the control of cell differentiation (RAX2, OR11H12, OR2M3, DDN, and GRIN3A
), transcription (CLOCK, IRF6, RAX2, TCFP2, and BCL6B), proliferation (SENP2, RBL1, CDC14B, and S100A13), cytoskeleton (DDN, MSN, and CTNNA1), metabolism (ADAM15, FUT3, ADM2, LTA4H, BDH2, and RAB5A) , and cell immune regulation (CRLF1, IL1RN, and MT1X) (Table 2).
Among them, GO:0004888 dominantly contains 33 transcripts encoding signal receptors, and these receptors could be further classified into several subgroups: OXTR, LOC431251 and SSTR3 belong to reproductive hormone receptors; CHRM2, ADRA2B, P2RX4, P2RY2, EDNRB2, GABRB2, GABRG2, LOC428961 and NPFFR2 function as receptors mediating neurotransmitters or neuropeptide; GRIN2B and GRIN3A
could modulate the efficiency of synaptic transmission; NTRK1 and NTRK2 belong to the receptor tyrosine kinase (RTK) family, and are involved with neurotrophin (GO:0005030--neurotrophin receptor activity; and GO:0043121--neurotrophin binding) (Table 5).