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| Brain region | Changes of neural plasticity | Mechanisms |
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| Hippocampus | Synaptic plasticity | (1) Triggering of LTD via ROS and NOS
(2) Impairment of LTP in presynaptic neurons
(3) Impaired synaptic transmission and plasticity in dentate gyrus area of rats
(4) Fine structural changes of synapses in CA1 region |
| Volumetric changes | (1) Hippocampal atrophy and neurons apoptosis
(2) White matter density decreased |
| Apoptosis | (1) A severe loss of neurons induced by activation of MAPK signaling pathways
(2) ER stress and oxidative stress |
| Misfolded/unfolded protein | (1) Increased production of ROS |
|
| Prefrontal cortex | Synaptic plasticity | (1) Increased density of the GABAergic neurons impair the network activity within PFC
(2) Increased neuronal death
(3) Activation of T-type Ca2+ channels in the MD |
| Activity in vmPFC and dlPFC | (1) Increasing the acetylcholine release by enhancing the activation of G protein |
| Immunoreactive cells and cytokine changes | (1) Upregulated expression of molecules such as VEGF, Hif-1, and Glut1
(2) PV cells loss induced by the NOX2-derived oxidative stress |
| Volumetric changes | (1) Increased neuronal death and ghost cells
(2) Tissue atrophy |
|
| Amygdala | Synaptic plasticity | (1) Decreased expression of NPY
(2) Increased expression of c-fos protein |
| Volumetric changes | (1) Smaller gray matter volume in the amygdala and decreased volume of the left amygdala
(2) Significant shrinkage of cell size and axonal degeneration of corticotropin-releasing factor-positive neurons |
|
| Signaling pathways | Upregulation of Abcc1, Abcc2, and Abcc4 mRNA expression at the BBB | (1) Regulated through Nrf2 signaling |
| Activation of BDNF-TrkB signaling pathway | (1) The circulating levels of BDNF increased |
| Enhancement of ERK1/2-CREB-BDNF signaling pathway | (1) The circulating levels of BDNF increased |
| Activation of STAT3 signaling pathway | (1) Phosphorylation of STAT3 |
| Triggering cAMP/PKA signaling pathway | (1) Increased release of CRF |
| Dysregulation of NMDARs-Wnt-catenin signaling | (1) Decreased expression of NMDARs |
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