Astrocytes (star-shapped cells that) are an often overlooked cells in the CNS.
Here they are depleted and disease gets worse
Inflammation and Demyelination in a Murine Animal Model of Multiple Sclerosis. Allnoch L, Baumgärtner W, Hansmann F.Int J Mol Sci. 2019;20(16). pii: E3922.
So lets get promote them?……. but maybe not
Neurotoxic potential (Nerve damaging) of reactive astrocytes in canine distemper demyelinating leukoencephalitis (Dog viral demyelination). Klemens J, Ciurkiewicz M, Chludzinski E, Iseringhausen M, Klotz D, Pfankuche VM, Ulrich R, Herder V, Puff C, Baumgärtner W, Beineke A.Sci Rep. 2019;9(1):11689
Its another example of cells being able to do good and bad things. Astrocytes are made for a reason and that is supporting brain health. One way is to help nerves and another way is to help create the blood brain barrier, which keeps stuff from the blood out of the brain. So there they are good but they can be made to make molecules that can kill nerves or make microglia kill nerves and there they are bad. This helps explains why drugs often have side effects. Cells can multi-task.
Within lesions cells do not behave the same
The landscape of myeloid and astrocyte phenotypes in acute multiple sclerosis lesions.Park C, Ponath G, Levine-Ritterman M, Bull E, Swanson EC, De Jager PL, Segal BM, Pitt D. Acta Neuropathol Commun. 2019 Aug 12;7(1):130. (FREE ARTICLE)
Therefore until there are special tools to get at individual astrocyte functions, in humans there are bound to be consequences if we take a blanket approach to targetting astrocytes
I read somewhere guys inhibited microglia with Metformin and it made things worse
Divergent Effects of Metformin on an Inflammatory Model of Parkinson’s Disease
https://www.frontiersin.org/articles/10.3389/fncel.2018.00440/full
>>Interestingly, metformin not only failed to protect against the LPS-induced death of dopaminergic neurons, but exacerbated the damage (29.6% of control value; Figures 7D,E).
(btw did you know the story behind MPTP? That guy, Barry Kidston, is a personal hero of mine, wish I were so smart)
Stars Are Not in Outer Space: Astrocytes Respond to Environmental Cues
https://www.cell.com/cell/fulltext/S0092-8674(18)31639-8?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS0092867418316398%3Fshowall%3Dtrue
Thanks I once heard that the A1 and A2 distinction is mushroom food but the authors just wanted to be like the Th1 Th2 and M1 and M2 crowd
Klemens, et al describe the pathophysiology of demyelination in canine distemper demyelinating leukoencephalitis. This is the likely mechanism by which canine distemper virus induces demyelination in multiple sclerosis as well.