Table 1. Effects of microglia ablation or inhibition on oligodendrogenesis and myelination.
Method(s) for microglia
ablation/inhibition |
Organism
and ROI |
Effects on
oligodendrogenesis |
Effects on myelination | Reference |
Csf1r−/− transgenic | P20 mouse CC and SVZ | High degree of OPC apoptosis; mature OL population reduced |
No noted effects on myelination |
(73) |
Intraperitoneal administration of minocycline to prevent microglia activation |
P5 rat SVZ | Increased OPC population but reduced premyelinating and mature OL numbers; no difference in OL-lineage proliferation labeling |
Number of MBP+ cells decreased |
(56) |
CSF1R inhibitor BLZ945 |
P20 and P40–P42 mouse WM | Reduced number of OLs in P20 CC |
P20: Reduced expression and labeling of myelin proteins in CC and cerebellum; decrease in % of myelinated axons; no difference in myelin thickness; P40–P42: no difference in PLP or MBP |
(13) |
Transgenic deletion of Igf-1 gene in CD11c+ microglia |
P21 mouse CC | No noted effects on oligodendrogenesis |
Decreased expression on Plp, Mag, and Mog; reduced myelin staining; thinner myelin sheaths |
(15) |
Csf1r−/− transgenic | 3-week rat CNS | Decrease of oligodendrocyte gene expression |
Reduced myelination in the CC; decrease of myelin- associated gene expression |
(72) |
Pediatric-onset leukoencephalopathy patients (homozygous CSF1R mutations) |
Human brain tissue (10 months to 25 years) |
No noted effects on oligodendrogenesis |
Periventricular white matter abnormalities; cerebellar and CC hypoplasia/atrophy |
(71) |
PLX5622 and PLX3397 (CSF1R inhibitors) |
8- to 10-week mouse CNS | Reduced OPC viability in vitro and ex vivo; regional reduction of OPCs in vivo |
No difference in mature OL populations or PLP labeling |
(74) |
(i) Blockade of Irf8 translation (ii) CSF1R inhibitor GW2580 (iii) Microglia expression of nitroreductase + actuator |
4 DPF zebrafish optic tectum and SC |
No difference in number or distribution of OLs |
Oligodendrocytes produced more sheaths and sheaths were shorter in length; increased incidence of ectopic myelination |
(50) |
Microglia ablation via Csf1r
double mutant |
10 DPF zebrafish SC | Reduced number of OLs | Reduced total myelinated area, increased number of myelin structure pathologies, and no difference in sheath length |
(40) |