Review Article
Neural Plasticity and Proliferation in the Generation of Antidepressant Effects: Hippocampal Implication
Table 2
Involvement of cAMP, Wnt/
-catenin, and mTOR-signaling pathways in major depression (MDD) and antidepressant treatment.
| Signaling pathways | Changes related to disease or treatment | Direct effect | | | Nontreated MDD (versus control) | Treated MDD (versus untreated) | | | | | Change | Region | Reference | Change | Region | Reference | Change | Reference |
|
cAMP/PKA | cAMP | AC (induced by FK, -AR, -AR) | |
[87–94] | cAMP | | [95, 96] | | | 5-HT1A-induced AC inhibition/ 5-HT4-induced AC stimulation | Human PFCx | [8, 97, 98] | cAMP (administration/degradation inhibition) AD-like effect | [99] | | | | | ↑ AC CB1-induced inhibition | | [100] | | | PKA | No data | ↑ PKA activity | | [101] | No data | CREB | CREB | |
[102–104] | ↑ CREB (protein, expression, activity) |
Hp, Cx |
[11, 103–110] | CREB viral expression in Hp AD-like effect | [44] | | CREB viral expression in Acb depression-like effect | [111] | Epac | Epac- | Hp, PFCx | [112] | No data | No data |
|
Wnt/-catenin | GSK- | GSK- | Hp | [113] | GSK-3β | Hp | [8, 10, 113–117] | GSK-3 inhibition AD-like and anxiolytic effect | [117–120] | GSK-3 knock in stress-induced depression | [121] | GSK-3β SNP ( T/C; rs334558) later onset of bipolar depression | [122] | GSK-3β SNP ( T/C; rs334558) antidepressant response | [123] | -catenin | β-catenin |
PFCx |
[124] | -catenin |
Hp | [8, 10, 26, 83, 113–117] | -catenin ko mice depression-like effect | [125] | -catenin OE mice AD-like effect | [126] |
|
mTOR | mTOR | mTOR, p70S6K, eIF4B, p-eIF4B | | [127–129] | p-mTOR/mTOR | PFCx | [27, 130] | Activation (NMDAr antagonists) AD-like effect | [27, 131] |
|
|
: increase; : decrease; AC: adenylyl cyclase activity; FK: forskolin; Hp: hippocampus; PFCx: prefrontal cortex; Acb: accumbens nucleus; OE: overexpressing.
|