1/13
A 🧵on our work on the role of #glia in #MECFS
frontiersin.org/articles/10.33…
Our paper explains why ME/CFS research may benefit from a closer look at the role of the immune system of the brain.
A 🧵on our work on the role of #glia in #MECFS
frontiersin.org/articles/10.33…
Our paper explains why ME/CFS research may benefit from a closer look at the role of the immune system of the brain.
2/13
Many things are known about the pathobiology of ME/CFS. There is evidence for (e.g.):
- immune dysfx
- metabolic / mitochondrial / peroxisomal dysfx
- endothelial / vascular dysfx
- dysfunction of the autonomous nervous system
and the CNS in general
Many things are known about the pathobiology of ME/CFS. There is evidence for (e.g.):
- immune dysfx
- metabolic / mitochondrial / peroxisomal dysfx
- endothelial / vascular dysfx
- dysfunction of the autonomous nervous system
and the CNS in general
3/13
How do the latter dysfunctions fit together and how do they conspire to cause the symptoms of ME/CFS?
Our hypothesis: these processes can affect a very important regulatory system of our biology: the innate immune system of our brain.
How do the latter dysfunctions fit together and how do they conspire to cause the symptoms of ME/CFS?
Our hypothesis: these processes can affect a very important regulatory system of our biology: the innate immune system of our brain.
4/13
This CNS immune system is based on a cellular unit called microglia, which cooperates with other glial cells (astrocytes, oligodendrocytes). This network coordinates the brain functions and is also important for the cooperation between peripheral and central immun system.
This CNS immune system is based on a cellular unit called microglia, which cooperates with other glial cells (astrocytes, oligodendrocytes). This network coordinates the brain functions and is also important for the cooperation between peripheral and central immun system.
5/13
Also, this neuroglial network
- regulates cerebral blood flow
- affects peripheral inflammation via the vagus nerve
- cooperates with mast cells
- helps regulate all functions broken in ME/CFS: motor fx, autonomous regulation, sleep, sensory gating, memory, mood & cognition
Also, this neuroglial network
- regulates cerebral blood flow
- affects peripheral inflammation via the vagus nerve
- cooperates with mast cells
- helps regulate all functions broken in ME/CFS: motor fx, autonomous regulation, sleep, sensory gating, memory, mood & cognition
6/13
We then examined if dysfunctional glia may explain the two most salient features of ME/CFS:
a)the clinical phenomenon of PEM
b)the reduced cerebral blood flow (CBF)
We picked ⬇️CBF over other pathological features because it is undisputed and present in all ME/CFS patients
We then examined if dysfunctional glia may explain the two most salient features of ME/CFS:
a)the clinical phenomenon of PEM
b)the reduced cerebral blood flow (CBF)
We picked ⬇️CBF over other pathological features because it is undisputed and present in all ME/CFS patients
7/13
We found that both features are intricately linked to glial functions, supporting a central role of this regulatory unit.
We then show that (and how) the other pathobiological pathways of ME/CFS (see tweet 2/13) also affect the functionality of the glial network.
We found that both features are intricately linked to glial functions, supporting a central role of this regulatory unit.
We then show that (and how) the other pathobiological pathways of ME/CFS (see tweet 2/13) also affect the functionality of the glial network.
8/13
Finally, we review the ME/CFS experimental record for evidence from studies (imaging, proteomics, transcriptomics, etc) for evidence of glial dysfunction.
Here, we identify many findings from different fields which suggest that the function of glia is affected in ME/CFS.
Finally, we review the ME/CFS experimental record for evidence from studies (imaging, proteomics, transcriptomics, etc) for evidence of glial dysfunction.
Here, we identify many findings from different fields which suggest that the function of glia is affected in ME/CFS.
9/13
For example, the CNS findings in ME/CFS:
-⬇️ neurovascular coupling
-⬇️ cerebral blood flow
-⬇️functional connectivity between brain areas
-⬆️intracranial pressure
-🔄cellular metabolism in several brain areas/nuclei
…can all be explained as manifestations of glial dysfx
For example, the CNS findings in ME/CFS:
-⬇️ neurovascular coupling
-⬇️ cerebral blood flow
-⬇️functional connectivity between brain areas
-⬆️intracranial pressure
-🔄cellular metabolism in several brain areas/nuclei
…can all be explained as manifestations of glial dysfx
10/13
We also point to a unique property of glia: they can shift between an “aggravated” and a more “quiescent” state:
- aggravation happens by any form of stress
- repeated activation makes the glia more prone to overreaction
- thus, the reactivity threshold can fluctuate
We also point to a unique property of glia: they can shift between an “aggravated” and a more “quiescent” state:
- aggravation happens by any form of stress
- repeated activation makes the glia more prone to overreaction
- thus, the reactivity threshold can fluctuate
11/13
We think that this may explain the typical PEM features:
- delayed onset
- typical duration of several days (to weeks)
- different individual threshold for PEM between patients
We think that this may explain the typical PEM features:
- delayed onset
- typical duration of several days (to weeks)
- different individual threshold for PEM between patients
12/13
Our explanations are not meant to replace or contradict other theories about ME/CFS, like mitochondrial dysfx, endothelial dysfx etc. Our theory only adds a layer which may provide a finer-grained understanding of these features. This is shown in one of our figures:
Our explanations are not meant to replace or contradict other theories about ME/CFS, like mitochondrial dysfx, endothelial dysfx etc. Our theory only adds a layer which may provide a finer-grained understanding of these features. This is shown in one of our figures:
13/13
For those who would like to read up on our theory in a digest version, here it is:
kinder-verstehen.de/wp-content/upl…
For those who would like to read up on our theory in a digest version, here it is:
kinder-verstehen.de/wp-content/upl…
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