Table 1.
Effects of CX3CR1 deficiency in different models of CNS diseases.
| Model | Time from injury | Deletion protective? | Effects of deletion | Reference |
|---|---|---|---|---|
| SCI | 5–35 days | Yes | ↑ hindlimb function, ↓ myelin and axon loss, ↑ CD45, ↓ IL-6, and iNOS | (181) |
| 42 days | No | Worsened locomotor function, ↓ myelin, ↑ infiltrating monocytes/macrophages | (189) | |
| pMCAo | 24 h | Yes | ↓ ischemic volume | (187) |
| tMCAo | 3 days | Yes | ↓ infarct size | (186) |
| 1–3 days | Yes | ↓ infarct size, ↓BBB breakdown, ↓ apoptosis, ↓microglia, and ↓IL-1β | (179) | |
| 24 h | Yes | ↓ infarct size, ↑ ramification in microglia, ↓ CD11b and CD68, ↑ CD45high, ↑Ym1, and ↓iNOS | (40) | |
| 72 h | Yes | ↓ infarct size, ↓ neurological deficit, ↓ apoptosis, ↓ IBA1, and CD45high, ↑ Ym1, ↓ iNOS, ↓ microglia proliferation, ↓ ROS, ↓ IL-1, IL-6, and TNF-α | (195) | |
| 43–60 days | No | ↑ microglia activation, ↑ IL-1β, and TNF-α, ↓ IL-4 and IL-10, worsens cognitive functions | (190) | |
| LPS | 4 days | No | ↑ TUNEL, ↑ IL-1β | (178) |
| PD | 7 days | No | ↑ loss Nissl-stained cells, ↑ loss TH-IR | (178) |
| ALS | 15–20 weeks | No | ↓ neuronal cell density, ↓ motor function, ↓ survival | (178) |
| AD | 28 days | No | ↑ IL-6 and TNF-α, ↑Mac2 (activated microglia), ↓ cognitive and memory deficits | (192) |
| 28 days | Yes | ↓ neuronal loss | (196) | |
| 28 days | Yes | ↓ Aβ deposition, = CD45, ↓GFAP, ↓ TNF-α and MCP-1/CCL2, ↑IL-1b, microglia more rounded, ↓ CD68, ↑ Aβ phagocytosis | (197) | |
| 28 days | Yes | ↓ Aβ deposition, ↑ Aβ phagocytosis, ↑ microglia proliferation, = neuronal injury | (198) | |
| Tau pathology | No | ↑ MAP phosphorylation, behavioral impairments, ↑ microglial activation, ↑IL-1b | (199) |
The role of the fractalkine receptor (CX3CR1) in CNS pathologies has been studied using cx3cr1-/- mice. In different disease models, including SCI, permanent ischemia (pMCAo), transient ischemia (pMCAo), lipopolysaccharide (LPS)-induced inflammation, Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), Alzheimer’s disease (AD), and Tau pathology. The results are often contrasting and depict a puzzling situation. A potential general hypothesis is that CX3CR1 deletion is protective in the early phases after acute injury, but becomes deleterious at later stages or in chronic conditions.