I injected a drug (subcutaneous in mice) and I noticed that there was an increase in number of microgias in the hippocampus (IBA positive cells). These microglias are more branched and non-reactive to MHC-II.
How should I interpret this increased in the number of branches and increased in the number of not activated microglia caused by a drug compared to control animals (which did not suffer intervention)? It can be interpreted as neuroprotection phenotype even if they have not suffered any inflammatory stimulus? Is it possible that microglia become more "resting" than those of the control animals that do not have inflammatory stimulus?
What was the drug, please? Or if you prefer, what type of drug? Was it a cholinersterase inhibitor?
If I interpret well your experiment, you inject subcutaneously and find a different phenotype of microglia in hippocampus, compared to controls injected with PBS. Is something like this?
Anyways, apart from the cause of the change of phenotype, there is a new way of looking at these cells when they are not resting. When they abandon resting state they may undergo quite a number of phenotypic and functional alternatives. Probably I cannot put the pdf of this publication here (not open access). If you ask the authors by e-mail they will send you (or anybody interested) this paper.
Alternatively activated microglia and macrophages in the central nervous system.
Franco R, Fernández-Suárez D.
Prog Neurobiol. 2015 Aug;131:65-86. doi: 10.1016/j.pneurobio.2015.05.003. Epub 2015 Jun 8. Review.
PMID:
26067058
There is also an excellent new paper out from Marie Eve Tremblay showing a new type of microglia (called "dark" microglia based on their EM appearance) that becomes abundant during pathological states such as chronic stress, aging, Alzheimer's, etc. They display signs of oxidative stress, but also have highly ramified, thin processes, so it sounds like they may be relevant for your question. See paper below:
Glia. 2016 May;64(5):826-39. doi: 10.1002/glia.22966. Epub 2016 Feb 5.
Dark microglia: A new phenotype predominantly associated with pathological states.
Bisht K1, Sharma KP1, Lecours C1, Gabriela Sánchez M1, El Hajj H1, Milior G2, Olmos-Alonso A3, Gómez-Nicola D3, Luheshi G4, Vallières L1, Branchi I5, Maggi L2, Limatola C2, Butovsky O6, Tremblay MÈ1.
http://www.ncbi.nlm.nih.gov/pubmed/26847266
http://www.ncbi.nlm.nih.gov/pubmed/26847266
Dear André
It may likely happen that whahever you find in your experimental conditions may help understanding the "new" possibilities of microglia.
It is the primary job of microglia to take up excessconcentrations of potassium and sodium as an adjacent neuron depolarizes to avoid destructive levels of the bases. If a neuron if over stimulated (your injection) then it makes sense that more are needed and branching allows the glial cell to respond more rapidly to rapidly firing neurons. Remember the theory of summation ?
Dear Andre,
A number of factors can activate/inactivate microglia. Responses of microglia may be different to infectious bacterial/viral vectors compared developmental physiological pruning of dendrites/spines. In my case in brain slices by using GABAA receptor and Glycine receptor blockers (by inhibiting synaptic inhibition) I activate microglia, as evident from their response of phagocytosis of neurons. I also see increased branching of microglia, and these branches seem to reach and phagocytose the dendrites of neurons. For details, please see Fig 9 in my following paper.
best wishes, Refik
Article Emerging Roles of Filopodia and Dendritic Spines in Motoneur...
Jane, with all due respect,
1. microglia are not the cells to be considering when suggesting a spatial buffering situation.
2. Summation has not a thing to do with anything in this thread
3. Please expound on the vast literature upon which I am sure you rest your hypothesis that an injection causes "overstimulation" of hippocampal neurons.
4. "More branching allows better response to rapidly firing neurons"?
Hi Andre,
What you describe as microglia becoming more "resting" than those of the control animals could be the result of thickening of branches (so more Iba1 immunoreactivity) making them more detectable. Its been referred to as hyper-ramified microglia. We have seen a similar phenotype (also MHC II negative) in an acclerated aging mouse model (Refer: https://www.researchgate.net/publication/262075668_Priming_of_microglia_in_a_DNA-repair_deficient_model_of_accelerated_aging?ev=prf_pub). Others have reported it as well. For instance: http://cercor.oxfordjournals.org/content/early/2012/06/16/cercor.bhs151.full. Please comment if what you see is comparable.
Article Priming of microglia in a DNA-repair deficient model of acce...
Hi Divya,
That's exactly what I saw in microglia.
Am going to read your article, it looks great and has great pictures! congratulations! I loved the 3D analysis of microglia !! I want to try this !!
And thanks for the reply!
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