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. 2019 Apr 18;10:220. doi: 10.3389/fpsyt.2019.00220

Figure 1.

Figure 1

The role of molecular genetic markers in cellular stress response. The interconnection between genes IGF2, MBL2, MEST, NR3C1, NR3C2, TSC22D3, and BDNF in the context of stress response is shown. Membrane-bound IGF2 induction by maternal distress is associated with nuclear NR3C2 induction (3). IGF2 shows similar changes in methylation levels with NR3C1 during age-related stress (4), FKBP5 during the development of preterm infants (30), and MEST in infertile males (31). MBL2 and FKBP5 upregulation has been associated with parental-nutrition-induced stress (32, 33). NR3C2 and NR3C1 interact to control gene expression during stress (8, 34). Nuclear NR3C1 (glucocorticoid receptor) seems to be a convergence point for FKBP5 (9, 35), NR3C2 (10, 36), MEST (11, 37), and IGF2 (4) action in stress. TSC22D3 is an established glucocorticoid signaling responsive gene that is regulated by NR3C1 (27, 38) and an NR3C2 target (28). BDNF is upregulated by IGF2 (39) in an Alzheimer’s disease mouse model, inhibited by NR3C1 (40) in neuron-like cells, and associated with high NR3C2 and low NR3C1 in high-cholesterol-diet rats (41). FKBP5 elevation is associated with BDNF suppression and improved anxiety, depression, and posttraumatic stress disorder conditions (42). Gene interaction analysis was performed using the Genomatix Pathway System (Genomatix.de).