In 2-month-old wild-type mice, seven days of PLX3397 at 290 mg/kg chow reduced IBA1-positive microglial counts by >90% in the hippocampus, cortex and thalamus versus vehicle chow (n = 4 per group). [1]
In postnatal retinal microglia, Axl knockout increased susceptibility to PLX3397, whereas CR3, CX3CR1 or Mer loss did not significantly lower the surviving fraction. Depletion therefore depends on the developmental and signaling context. [2]
An independent seven-day dietary study compared 660 with 75 mg/kg PLX3397 chow. Brain microglial density declined, while several heart immune-cell populations also decreased. This active-comparator design supports caution when attributing systemic PLX3397 effects solely to microglial depletion. [3]
Adult brain microglial depletion
Animal study · 2-month-old wild-type mice; hippocampus, cortex and thalamus; n = 4 per group [1]
Seven days of dietary PLX3397 reduced IBA1-positive microglia by >90% across the three regions versus vehicle chow. Microglial-marker transcripts also decreased. This design measures adult brain depletion, not kinase selectivity.
Conditions shared by the study groups
- Route
- Oral, in diet
- Frequency
- Dietary exposure
- Treatment course
- 7 days
- Vehicle
- AIN-76A standard chow
- PLX3397 versus vehicle chow
- Model: 2-month-old wild-type mice; n = 4 per group
- Reported limits: No salt or lot information in retrieved main text.
Methods and source locations
Compound reported in the paper: Pexidartinib (PLX3397); Compound label in the paper: PLX3397
Results apply to the reported Plexxikon PLX3397 preparation and mouse model.
Results: CSF1R inhibitors dramatically reduce microglia numbers in the adult brain; Figure 2A-D and caption; Materials and Methods: Compounds, Immunostaining, Confocal microscopy
IBA1-positive cell bodies in a 10X field of view in hippocampus, cortex and thalamus: Automated IBA1 cell-body counts; n = 4 per group; Figure 2C and associated Results. Operator is author-reported, not estimated from bars. — Results: CSF1R inhibitors dramatically reduce microglia numbers in the adult brain; Figure 2A-D and caption; Materials and Methods: Compounds, Immunostaining, Confocal microscopy
PLX3397 versus vehicle chow · Results: CSF1R inhibitors dramatically reduce microglia numbers in the adult brain; Figure 2A-D and caption; Materials and Methods: Compounds, Immunostaining, Confocal microscopy
Axl-dependent survival of developmental retinal microglia
Animal study · Postnatal mouse retina across CX3CR1-GFP/+, Bax KO, CX3CR1 KO, CR3 KO, Mertk KO, Axl KO and Mertk/Axl double-KO genotypes; both sexes [2]
Axl knockout increased depletion relative to CX3CR1-GFP/+ controls, while CR3, CX3CR1 or Mertk knockout did not significantly reduce the surviving fraction. Mertk/Axl double knockout had no additive effect over Axl loss. This supports developmental-state dependence of survival after CSF1R inhibition.
Conditions shared by the study groups
- Route
- Intraperitoneal
- Frequency
- Daily
- Treatment course
- P4-P6 dosing; P7 collection
- Vehicle
- Corn oil and 10% DMSO
- PLX3397 across genotypes with matched vehicle controls
- Model: n = 17 CX3CR1-GFP/+; 5 Bax KO; 11 CX3CR1 KO; 5 CR3 KO CX3CR1-GFP/+; 9 Mertk KO; 8 Axl KO; 7 Mertk/Axl dKO; at least 2 litters per genotype
- Reported limits: Caption gives n by genotype, not separately by treatment arm; preserve its meaning. Historical control data are not newly independent observations.
Methods and source locations
Compound reported in the paper: Pexidartinib (PLX3397); Compound label in the paper: PLX3397
Reported developmental retinal microglia experiment; supplier citation does not certify any current lot.
Results: Axl promotes microglial survival in the absence of CSF1R signaling; Figure 6A-C and caption; Key resources table; Methods: Animal husbandry and procedures, Mouse strains, Dissociation/FACS/flow cytometry
Ratio of microglial density among singlets in PLX-treated retinas to genotype-matched vehicle controls: Flow cytometry: CD45+ CX3CR1-GFP+ or CD45+ CD11b+ microglia/singlets. Welch ANOVA W(6,18.55) = 16.53, p < 0.0001; Dunnett T3 comparisons. Figure 6C; bars ± SEM. No exact ratios inferred. — Results: Axl promotes microglial survival in the absence of CSF1R signaling; Figure 6A-C and caption; Key resources table; Methods: Animal husbandry and procedures, Mouse strains, Dissociation/FACS/flow cytometry
PLX3397 across genotypes with matched vehicle controls · Results: Axl promotes microglial survival in the absence of CSF1R signaling; Figure 6A-C and caption; Key resources table; Methods: Animal husbandry and procedures, Mouse strains, Dissociation/FACS/flow cytometry
Brain depletion and peripheral immune effects with an active chow comparator
Animal study · Male mice, 11-13 weeks, C57BL/6J background; wild-type and CX3CR1-GFP/+ animals; brain and heart [3]
The same 7-day dietary comparison demonstrated brain microglial depletion and reductions in selected heart immune populations. The comparator contained 75 mg/kg PLX3397, so the experiment does not establish effects relative to drug-free chow.
Conditions shared by the study groups
- Route
- Oral, in diet
- Frequency
- Dietary exposure
- Treatment course
- 7 days
- Vehicle
- Chow
- 660 versus 75 mg/kg PLX3397 chow
- Model: Male mice aged 11-13 weeks; n = 4-6 for Figure 1; n = 3 for Figure 4
- Reported limits: No conversion to body-weight dose. No drug-free arm inferred from the generic Control labels in figures.
Methods and source locations
Compound reported in the paper: Pexidartinib (PLX3397); Compound label in the paper: PLX3397
Reported 7-day high-dose versus low-dose chow comparison; cannot establish systemic inertness or effects relative to drug-free controls.
Results Sec2 and Sec5; Figure 1a-j and Figure 4a-i with captions; Methods Sec11-Sec12, Sec16-Sec19
Microglia per field of view in cortex and hippocampus: CX3CR1-GFP immunohistochemistry; percentages explicitly reported in Results, not estimated. Figure 1 caption: n = 4-6; mean ± SEM; unpaired Student t test. — Results Sec2; Figure 1g-j and caption; Methods Sec11-Sec12
Recovered heart immune populations: Flow cytometry; n = 3; mean ± SEM; unpaired Student t test. Figure 4 plots cells/mL. No exact counts inferred. — Results Sec5; Figure 4a-i and caption; Methods Sec11-Sec12 and Sec18-Sec19
660 versus 75 mg/kg PLX3397 chow · Results Sec2 and Sec5; Figure 1a-j and Figure 4a-i with captions; Methods Sec11-Sec12, Sec16-Sec19
