In a meeting I watched today, microglia priming was mentioned in #LongCovid and #ME/CFS. It’s important to clarify what “microglia priming” means. Microglial priming does not mean that after a trigger has “cleared” microglia remain perpetually activated
Conversation
Replying to
2/ Instead, microglia priming goes like this 👉 When microglia or other glial cells detect #infection, injury, or inflammatory mediators, they enter a state of activation in which they change morphology and release their own neuroexcitatory inflammatory mediators
3
21
149
3/ Then, after activating, they retain a “primed” functional state which causes an even more robust response to *subsequent* infectious/immune/#inflammatory challenges. And as cells, microglia live long lives (they are not replaced as often as many other cell types)
1
14
140
4/ So microglia can remain in a “primed” state over long periods of time, but there needs to be subsequent infectious or inflammatory events that drive primed microglial cells into a hyperactivated state
2
16
145
7/ If the vagus nerve senses #inflammation (especially cytokine activation) in these other body sites, it signals to the brainstem in a manner that generates a “mirror response” of microglia activation in the brainstem itself
1
18
148
8/ Inflammatory event in the periphery of the body that can be sensed by the vagus nerve to cause this microglia “mirror” response in the brainstem include acute/ongoing infections, #microbiome dysbiosis, injury etc.
3
16
134
9/ Again it is the collective nature of these different microglia-activating events that leads to a primed state. The first “hit” makes the activated microglia respond more dramatically to the second, causing more profound #neuroinflammation
1
16
139
10/ That’s why it’s no suprise that many #ME/CFS and even #LongCovid patients report multiple “hits” in their cases. A #brain injury and an infection. Or gut micorbiome dysbiosis and mold exposure. Each of these might converge to drive microglial priming
4
27
199
11/ To better understand what I’m saying, watch ’s recent talk at the Seminar Series where he explains how infectious/immune/gut microbiome/vagus nerve signaling can converge on microglia activity/priming in the dorsal brainstem:
7
41
208
12/ This matters for #treatment in LongCovid or ME/CFS. We can shut down microglial signaling with inhibitory drugs. But if we also clarify the infectious/inflammatory/injury-related events that prime microglia in the first place, and treat those issues too, patients cld benefit
11
26
199