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Brain inflammation appears common in autism

adreno

PR activist
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4,841
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natasa778

Senior Member
Messages
1,774
Whoda thunk it? ;)

Esp since this has been known for 9 years ... good to have further confirmation, though I'd much rather the money is spent on exploring treatment options

here is the actual study

“… These data provide support for a mechanistic connection for viral-infection hypotheses for autism with neural over-growth hypotheses through the novel identification of exaggerated M2 activation states in autism brain tissue.

…. We observe, for the first time, that M2-activation state microglia genes, in particular, are altered in autism, potentially driven by type I interferon responses…”

http://www.nature.com/ncomms/2014/141210/ncomms6748/full/ncomms6748.html


Any thoughts on this M2 thingy?
 

natasa778

Senior Member
Messages
1,774
I have no ideas just yet but its intriguing enough I might look into this after Xmas. I would love to read what others think about this.

answering my question, sort of

http://link.springer.com/article/10.1007/s00281-013-0382-8/fulltext.html

Microglia can exhibit different phenotypes that have some of the characteristics of M1- and M2-phenotypes, but they are also highly plastic cells and may transition between different states depending on both local and systemic influences.

...
The signalling of systemic inflammation to the CNS, arising as a consequence of injury or disease, is part of normal homeostasis; it takes place across an intact blood-brain barrier and does not lead to damage of the neurons of the CNS. Although most of what we know about signalling from the peripheral immune system to the brain has been studied in rodents, experimental studies in humans provide evidence for similar effects of systemic inflammation. LPS challenge in humans leads to fever and neuropsychological symptoms. For example, low-dose endotoxin in healthy volunteers reduced declarative memory performance that was inversely correlated with cytokine increases [58] and increased symptoms of depression [59]. Other clinical symptoms include fatigue and decrease in social interest. Similar findings have been described following influenza H1N1 virus infection; individuals reported symptoms of anxiety and depression up to 1 year after the infection [60]. The use of biologicals as therapeutic agents has also provided valuable insight, and it is well known that peripheral injection of β-interferon leads to flu-like symptoms in patients with multiple sclerosis, that α-interferon therapy in patients with hepatitis C may lead to serious symptoms of depression in some individuals and that anti-tumour necrosis factor-α (anti-TNF) therapy in patients with psoriasis can lead to improvements in mood [61]. There are likely multiple systemic inflammatory mediators that impact on innate immune cells in the CNS, leading to changes in behaviour.
The regulation of the microglia phenotype by the microenvironment of the CNS appears to be an important part of CNS immune physiology.

...
Most tissue macrophages, following the appropriate stimulus, can polarize into M1 and M2 or M2-like phenotypes [66]. Classical activation and M1 polarization require interferon-γ (IFN-γ) combined with TLR4 signalling and are characterized by increased expression of pro-inflammatory mediators and effectors enabling phagocytosis and killing of pathogens. Alternative activation and M2 polarization occur in response to IL-4 and are distinguished by increased expression of transforming growth factor-β (TGFβ), IL-10, scavenger receptor CD206, MS4A4a/6A and fibrinogenic and coagulation factors, enabling regulation of wound healing, tissue repair, collagen formation and recruitment of Th2 cells. ...

http://link.springer.com/article/10.1007/s00281-013-0382-8/fulltext.html


... The data thus suggest that the normal homeostatic signalling from the peripheral immune system to brain is distorted in the diseased brain and leads to the generation of a response in the brain that can increase disease symptoms, increase neuronal loss and accelerate disease progression. The primed microglia now produce a maladaptive response during systemic inflammation.


Word 'primed' probably being the key in more than just autism ...
 
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natasa778

Senior Member
Messages
1,774
continuing from the last sentence above wrt 'priming' and subsequent reactivity

Even in the absence of clinical symptoms following a systemic challenge, there is increased axon injury associated with inducible nitric oxide synthase (iNOS) induction in microglia [86]. There was, however, significant heterogeneity in the appearance of the lesions after LPS challenge, with pronounced induction of axon injury in some and minimal axon injury in others. Laser dissection of individual lesions and further characterization showed that lesions with ongoing axon injury were associated with pro-inflammatory cytokine mRNA profile and iNOS synthesis, while the lesions with no or limited axon injury were dominated by the cytokine IL-10 [86]. These data show that the local regulation by the CNS microenvironment plays an important role in response to the systemic challenge.
 

Wally

Senior Member
Messages
1,167
I have no ideas just yet but its intriguing enough I might look into this after Xmas. I would love to read what others think about this.
@alex3619,
I thought the article linked below might be of interest to you when putting together your "after" Xmas reading list.
There is increasing confusion about the meaning of the terms inflammation, neuroinflammation, and microglial inflammation. We aim in this review to achieve greater clarity regarding these terms, which are essential for our understanding of the role of microglia in CNS inflammatory conditions.
See, www.sciencedirect.com/science/article/pii/S0014579311006351?_rdoc=1&_fmt=high&_origin=gateway&_docanchor=&md5=b8429449ccfc9c30159a5f9aeaa92ffb