Hi!

You could try to deplete microglia using injection of liposome-encapsulated clodronate

"There are five methods being used for the ablation of microglia in vivo or in cultured brain slices. (1) One method involves the use of CD11b-HSVTK mice in which the herpes simplex virus thymidine kinase (HSVTK) is placed under the control of the CD11b promoter expressed exclusively by microglia in the brain [56]. Thymidine kinase converts ganciclovir into cytotoxic kinases leading to cell suicide. Thus, ganciclovir exposure can serve as an inducible cell suicide technique in HSVTK-expressing microglial cells in transgenic CD11b-HSVTK mice. (2) A second method involves the use of DTR mice in which the human dipthera toxin receptor (DTR) is expressed under the control of CD11b [57]. Human DTR expressing microglial cells can be selectively ablated by localized injection of the dipthera toxin in the mice. (3) A third method involves the use of knockout mice that lack the hematopoietic-lineage specific transcription factor resulting in a lack of mature hematopoietic cells including microglia [58, 59]. However, the mice die by late gestation or shortly after birth. (4) A fourth method involves the use of CSF1R knockout mice. CSF1R knockout mice in which a null mutation in a macrophage-specific receptor, the colony stimulating factor-1 receptor (CSF1R), results in effective elimination of brain microglia embryonically and postnatally [60]. Interestingly, these mice are viable for up to the third postnatal week. (5) The last method involves ablation using clodronate. Clondronate can function as an intracellular mediator of apoptosis"

You can get more information from this reference

http://www.hindawi.com/journals/np/2013/456857/

You are absolutely right Hatem. However, concerning points (1) to (4), ablation of microglia is not brain region-specific (contrary to point (5) and Clothide's answer).

Low dose naltrexone, melatonin, NE aplha blocker prazosin, doxazosine, estradiol E2, Pulsatile GnRH, CRH antagonist

Inhibition vs. ablation is a quite a different issue. The former assumable prevents microglial functions, while the latter leaves dead microglia to cause trouble in brain. Unfortunately there is no specific way to exclusively INHIBIT microglia in specific brain regions. Minocycline etc. are not microglia-specific inhibitors - they do inhibit microglial activation/ pro-inflammatory functions, but also have direct neuroprotective effects and target signaling pathways in other cell types. We still have plenty to do to get more specific ways to manipulate microglia!

I have heard of people inhibiting microglia by targeting their mannose receptor. I am sorry but I don't remember where I heard it from. They were testing for the different effects of M1 and M2 microglia.

Hi, that's a good question!

If you want to deplete microglia, i think you can use an antibody block of function, such as the anti-MAC-1 saporin-conjugated, delivered directly in a specific brain region using an osmotic pump.

Nevertheless, the better manner to decrease/inhibit microglial effects will be to inhibit these cells rather than to kill them ! The question is always opened .......

Thanks to all that replied. Gancyclovir injected into a spcific nucleus in TK(MT-30) mice might be the best option. The nucleus I want to study is quite small so I'm not keen to do the liposomal clodronate experiment. The CSF-R1 is an interesting way to go but it appears all of the available drugs are only soluble in DMSO... not a great option for in vivo work. Does anyone know of a commercially available CSF-1 antagonist/blocker?

Hi Catherine! Did you finally get inhibition of Microglia in any specific brain region? Most likely you are already aware about Neuron paper published by Kim Green lab in your same institution. They found that administration of CSF1R inhibitors eliminates 99% of microglia from CNS. Surprisinly, mice without microglia are healthy, happy and they have no deficits in behavior or cognition. 

is that true that CSF1R inhibitors , inhibit also cKit. DO they have then any effect on neurogenesis?

Hi Catherine M Cahill, you can deplete microglia using CSF-1R inhibitor BLZ945 (provided by Novartis, Basel, Switzerland) CSF-1 antagonist/blocke here one of then you dissolve it in 20% (2-hydroxypropyl)-β-cyclodextrin (Sigma-Aldrich, Taufkirchen, Germany). A dose of 200 mg/kg bodyweight was used. In adult (8–10 weeks old) mice, BLZ945 was applied by oral gavage for 7 consecutive days ( see Marco Prinz paper 2017 -https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5951721)

In the main time, I don't recommend clodronate-encapsulated liposomes for in vivo model since intravenous administration efficiently depleted circulating monocytes according to Sunderkötter et al., (2004) and since they did not pass the blood brain barrier this technique could be used to ablate circulating monocytes without affecting CNS-resident macrophage populations.However, if you are planing to do Ex-vivo culturing such as (Organotypic hippocapla slice culture) to deplete microglia is better to use clodronate-encapsulated liposomes.

Article Herbal Compounds Play a Role in Neuroprotection through the ...

... the PLX-5622, a CSF1R inhibitor, can also help you for inhibiting microglia.