Table 2.
Summary of literature evidence for the regulation of KCC2 expression upon paradigms of environmental challenges performed at either prenatal or postnatal developmental stages.
| Age | Environmental challenge | Duration | Effect | Brain region | Species | Sex | Reference | |
|---|---|---|---|---|---|---|---|---|
| Prenatal | GD9 | Maternal immune activation (PolyI:C) | Acute | ↓KCC2 (PND20-90), ↑ NKCC1 (E17) | Cortex | Mouse | Mix | [64] | 
| GD14-21 | Maternal restraint stress | Chronic (7 days) | ↓KCC2 (PND22-40),↑KCC2 transient (PND21), ↓NKCCl transient (PND14) | Hippocampus | Rat | NS | [104] | |
| GD15 | Maternal restraint stress or betamethasone i.p. (2x0,4mg/kg) | Acute | ↓KCC2 (PND7-15) | Cortex | Rat | Mix | [105] | |
| GD16-PND14 | Environmental enrichment | Chronic (20days) | ↑KCC2 (PND2) | Forebrain and hippocampus | Mouse | Both | [148] | |
| Postnatal | PND1-21 | Maternal separation | Chronic (21days) | ↓KCC2 (PND35–38), = NKCC1 | Hippocampus | Mouse | Male | [109] | 
| PND2-14 | Maternal separation | Chronic (13days) | ↑KCC2 (PND40), ↑NKCCl (PND14) | Hippocampus | Rat | Mix | [110] | |
| PND4-6 | Maternal separation plus saline injection | Chronic (3 days) | ↑KCC2 (PND10 - males only) | Hippocampus | Rat | Both | [111] | |
| PND21-28 | Restraint stress | Acute | ↓KCC2 activity | Paraventricular nucleus | Rat | Male | [115] | |
| 8–10 weeks | Restraint stress | Chronic (14days) | ↓KCC2, ↓pKCC2ser940 | Hippocampus | Mouse | Male | [112] | |
| 8–11 weeks | Forced administration of water | Chronic (21days) | ↓KCC2, ↓pKCC2ser940, ↑NKCCl | Hippocampus | Mouse | Female | [114] | |
| 12 weeks | Restraint stress | Acute | ↓KCC2, ↓pKCC2ser940 | Paraventricular nucleus | Mouse | Male | [113] | |
| Adult | Exercise after spinal cord transection at T12 | Chronic (7-28days) | KCC2/NKCC1 ratio restored | Spinal cord | Rat | Female | [145] | |
| Adult | Exercise after spinal cord transection at T12 | Chronic (23days) | KCC2/NKCC1 ratio restored | Spinal cord | Rat | Female | [144] | 
GD (gestational day); PND (postnatal day); NS (not specified). Arrows indicate either increased (↑) or decreased (↓) expression, while (=) indicate that no changes were found. Only KCC2 and NKCC1 variations, when indicated, have been reported.