Fig. 4: Metabolomics reveals altered glutamate, pyrimidine, and purine pathways related to sex and stress condition.

A The set of regulated metabolites in the male vs female comparison between NS and LBN conditions, with a dedication amount of specific regulated metabolites in only NS or only LBN conditions: BLA: 34.67%, 26 out of 75 metabolites, dHIP: 34.33%, 23 out of 67 metabolites, vHIP: 39.39%, 26 out of 66 metabolites. B Metabolite Set Enrichment Analysis (MSEA) revealed different pathways of interest in the BLA, dHIP, and vHIP. 1) purine metabolism was significantly regulated in NS (BLA: Holm test; p = 1.28^e−6; enrichment ratio (ER) = 7.32, dHIP: Holm test; p = 1.21^e−10; ER = 9.68, vHIP: Holm test; p = 3.8^e−9; ER = 8.81) and LBN (BLA: Holm test; p = 1.43^e−8; ER = 8.09, dHIP: Holm test; p = 2.02^e−9, ER = 10.24, vHIP: Holm test: p = 9.33^e−9, ER = 8.33). 2) pyrimidine metabolism was significantly regulated in LBN in the BLA (Holm test; p = 0.021; ER = 6.23), but not in NS (Holm test; p = 0.13; raw p-value = 0.0017; ER = 5.48), but not in the dHIP and vHIP. 3) glutamate metabolism; the pathway “alanine, aspartate and glutamate metabolism” was significantly regulated only in the BLA in NS (Holm test; p = 0.028; ER = 7.63), but not in LBN (Holm test; p = 0.33; raw p-value = 0.0042; ER = 5.79). The “arginine biosynthesis” was significantly regulated only in the vHIP in LBN (Holm test; p = 0.019, ER = 11.87), but not in NS (Holm test; p = 1, raw p-value = 0.039, ER = 6.23). Panels A and B represent female NS (n = 10, female LBN (n = 10), male NS (n = 10), male LBN (n = 11).