Inflammation Discovered in Autism

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Inflammation Discovered in Autism

Postby majadj » Sun Dec 21, 2014 3:18 pm

Downstream Inflammation Discovered in Autism

In the largest RNA sequencing of brain tissue from persons with autism that has been conducted to date researchers have discovered that the brains of individuals with autism have an overactive inflammatory process related to microglial cells, relative to persons without autism.

There are currently FDA-approved drugs that reduce M2 activation, such as the dementia drug nicergoline (Sermion, Pfizer Inc), that have been shown to have a neuroprotective effect, but more research is needed to determine whether reduction of the activation is what is needed in autism. ... c=175219HJ

Nicergoline (SERMION)

An ergot derivative that has been used as a cerebral vasodilator and in peripheral vascular disease. It has been suggested to ameliorate cognitive deficits in cerebrovascular disease.
Further studies indicate that nicergoline can enhance glutamate re-uptake and protect the brain against ischaemia (lack of blood flow).
Nicergoline has a broad spectrum of action:
- as an alpha(1)-adrenoceptor antagonist, it induces vasodilation and increases arterial blood flow;
- it enhances cholinergic and catecholaminergic neurotransmitter function
- it has neurotrophic and antioxidant properties.

A recent study in Italy showed that nicergoline can also have a neuroprotective effect
Nicergoline, a drug used for age-dependent cognitive impairment, protects cultured neurons against β-amyloid toxicity ... d-toxicity
And, the most importante:
Protective effects of nicergoline against neuronal cell death induced by activated microglia and astrocytes. ... t=Abstract

Medications for the treatment of peripheral vascular disease (peripheral vasodilators), like Redergin (Dihydroergotoxine) and Trental (Pentoxifylline) have been allrady used for autism.
Never heard that someone tried Sermion.
Maybe it is worth of trying.

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Re: Inflammation Discovered in Autism

Postby kulkulkan » Mon Dec 22, 2014 2:02 pm

Isn't M2 activation a good thing (anti-inflammatory)?

One approach could be to reduce M1 activation or address whatever is the underlying source causing it (which in turn is causing M2 response to remediate). From wiki, it seems M1 increase IL12 and lowers IL-10 response; whereas M2 does the exact opposite.

From the original study (linked in another thread).

Type I Interferon responses in the brain are classically attributed to viral infections that can produce M1 activation states in microglia (26). Accordingly, mod5 also shows enrichment for GO terms ‘defense response to virus’ (Phypergeometric=6.83 × 10−17) and ‘cytokine-mediated signalling pathway’ (Phypergeometric=6.31 × 10−16; Supplementary Data 13e). In opposition to M1-activated microglia, M2 responses are responsible for mediating anti-inflammatory remediation responses to damage caused by viral infections. M2 microglial cells also secrete ​brain-derived neurotrophic factor (​BDNF), increase the production of neural progenitor cells and promote myelination (27, 28, 29). These data provide support for a mechanistic connection for viral-infection hypotheses (30) for autism with neural over-growth hypotheses (31) through the novel identification of exaggerated M2 activation states in autism brain tissue.

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Re: Inflammation Discovered in Autism

Postby majadj » Mon Dec 22, 2014 4:06 pm

Well, it seem`s more complicated...

"... 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. This process may drive changes in neural progenitor cell proliferation and connectivity with resultant altered activity-dependent neural expression profiles in post-natal development..." ... s6748.html

"...There are a number of things that will activate M2 microglia ― type 1 interferon is one of them," explained Dr Arking, who is associate professor in the McKusick-Nathans Institute for Genetic Medicine at the Johns Hopkins University School of Medicine.
"All we can say is that the M2 are activated, and this activation seems to be a downstream consequence of the primary cause of autism..." ... c=175219HJ
Then, the Sermion was mentioned...

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Re: Inflammation Discovered in Autism

Postby luis » Fri Nov 06, 2015 3:08 pm

I haven't read this topic yet. Interesting.

Has anyone tried Sermion ?

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