Mitochondrial deficits in autism and impaired immune function

[natasa778]

Children with autism experience deficits in a type of immune cell that protects the body from infection. Called granulocytes, the cells exhibit one-third the capacity to fight infection and protect the body from invasion compared with the same cells in children who are developing normally. The cells, which circulate in the bloodstream, are less able to deliver crucial infection-fighting oxidative responses to combat invading pathogens ...

The researchers also found that the mitochondria in the granulocytes of children with autism consumed far less oxygen than those of the typically developing children ...

... "The response found among granulocytes mirrors earlier results obtained with lymphocytes from children with severe autism, underscoring the cross-talk between energy metabolism and response to oxidative damage," said Cecilia Giulivi, professor in the Department of Molecular Biosciences in the UC Davis School of Veterinary Medicine and the study's senior author.

"It also suggests that the immune response seems to be modulated by a nuclear factor named NRF2," that controls antioxidant response to environmental factors

http://www.sciencedaily.com/releases/2014/05/140508172310.htm

 

[alex3619]

Interesting.

 

[natasa778]

I am looking at environ factors that can influence/downregulate NRF2, and can't get further than retroviruses (surprise, surprise). Ideas?

Minocycline to the rescue?

We show here that minocycline delays neurodegeneration in ts1-infected mice, and that it prevents death of cultured astrocytes infected by ts1 through attenuating oxidative stress, inflammation and apoptosis. ... In addition, minocycline prevents death of primary neurons when they are cocultured with ts1-infected astrocytes, through mechanisms involving both inhibition of oxidative stress and upregulation of the transcription factor NF-E2-related factor 2 (Nrf2), which controls cellular antioxidant defenses. We conclude that minocycline delays retrovirus ts1-induced neurodegeneration involving antioxidant, anti-inflammation and anti-apoptotic mechanisms.

Attenuation of oxidative stress, inflammation and apoptosis by minocycline prevents retrovirus-induced neurodegeneration in mice

 

[taniaaust1]

Maybe it is this genetic weakness which causes more autism to be seen among the children at least of those who have ME/CFS if my observations on this have been correct (I think autism is a lot higher among our children). Maybe many of us are carrying a gene affecting these immune cells?

 

[Marco]

I am looking at environ factors that can influence/downregulate NRF2, and can't get further than retroviruses (surprise, surprise). Ideas?

Minocycline to the rescue?



Attenuation of oxidative stress, inflammation and apoptosis by minocycline prevents retrovirus-induced neurodegeneration in mice

Insulin resistance?

Role of nuclear factor (erythroid-derived 2)-like 2 in metabolic homeostasis and insulin action: A novel opportunity for diabetes treatment?

However, in mammals, a number of studies have actually shown that insulin signaling is required for Nrf2 activation[45,46]. Interestingly, Nrf2 function was found to be defective in aged mice[47] and aging is usually accompanied by insulin resistance. Whether impaired insulin signaling blunts Nrf2 function or the reverse in mammals remains to be examined.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3258535/

 

[lansbergen]

From, the abstract http://pediatrics.aappublications.org/content/133/5/e1405

Higher oxidative stress in cells of children with autism was evidenced by higher rates of mitochondrial reactive oxygen species production (1.6-fold), higher mitochondrial DNA copy number per cell (1.5-fold), and increased deletions.

 

[natasa778]

Maybe it is this genetic weakness which causes more autism to be seen among the children at least of those who have ME/CFS if my observations on this have been correct (I think autism is a lot higher among our children). Maybe many of us are carrying a gene affecting these immune cells?

Possible, but I very much doubt it is about them or 'us carrying a genetic weaknes' - given the number of genetic studies all coming up empty (ie one would expect it to have been picked up by now). More likely imo that something is actively interfering with its function ...

 

[natasa778]

Looking into things that regulate/influence Nrf2, I have come across this novel drug - has been in use for many decades in Russia, now being repackaged and re-marketed it seems (but only to Central and East Eu countries http://www.bachpharma.com/origins.php ?? )

Bach’s researchers have discovered the Mechanism of Action of its drug platform Monosodium Luminol GVT®.

Data from published studies shows that GVT®:

1. Regulates the activity of macrophages and synthesis of pro-inflammatory (IL-1, IL-6, TNF-alpha) and anti-inflammatory (IL-10) cytokines
2. Increases the level of immunoglobulins (IgM, IgA) in their failure, normalizes affinity immunoglobulin
3. Regulates the proliferative activity of subpopulations of T lymphocytes (T helper, T-killers)
4. Regulates the cytotoxic activity of NK cells
5. Has a stimulating effect on the phagocytic activity of neutrophils during its initial deficit
6. Regulates the synthesis of interferon alpha and gamma
7. Has antioxidant effect
8. Regulates the repair of damaged tissue
9. Regulates Nrf2 with increased production of glutathione (GSH) and thioredoxin

Monosodium Luminol GVT® has powerful effects on multiple pathways and networks:

• Restores mitochondrial membrane potential when mitochondria is under stress, and also prevents mitochondrial-induced cell death
• Relatively non-toxic, well absorbed, can be taken orally, rapidly excreted, can get into the brain by passing through the blood brain barrier
• Prevents oxidative stress, both by scavenging free radicals and by regulating Nrf2 with increased production of glutathione (GSH) and thioredoxin
• Reacts with peroxinitrite thereby preventing protein nitration and oxidation in microglia and preventing microglia-induced neuronal damage
• An iron and other heavy metal chelator and thereby prevents iron-catalyzed oxidative damage
• Decreases intracellular reactive oxygen species (ROS) levels in astrocytes and other cell types under various stress conditions

 

[Marco]

Looking into things that regulate/influence Nrf2,

Can't vouch for the accuracy of this but someone has put a lot of leg work in :

The pivotal role of Nrf2. Part 2 – foods, phyto-substances and other substances that turn on Nrf2

http://www.anti-agingfirewalls.com/...ances-and-other-substances-that-turn-on-nrf2/

I'm off to whip up a little curcumin, piperine and ginger concoction!

 

[natasa778]

Insulin resistance?

Interesting that this Russian drug I just posted about has been looked into for this:

An inflammation in adipose tissue study. Impact on insulin resistance and glucose tolerance with gavage administration of GVT® (GVT®) in FVB/N mice

http://www.bachpharma.com/indications_metabolic_syndrome.php

There was some talk recently about adipose tissue in ME/CFS if I remember correctly?

 

[Marco]

Interesting that this Russian drug I just posted about has been looked into for this:

An inflammation in adipose tissue study. Impact on insulin resistance and glucose tolerance with gavage administration of GVT® (GVT®) in FVB/N mice

http://www.bachpharma.com/indications_metabolic_syndrome.php

There was some talk recently about adipose tissue in ME/CFS if I remember correctly?

Metabolic disorders, oxidative stress, mito dysfunction and neuroinflammation do all appear to be linked although how closely is debatable :

Maternal obesity, diabetes associated with autism, other developmental disorders

A major study of the relationships between maternal metabolic conditions and the risk that a child will be born with a neurodevelopmental disorder has found strong links between maternal diabetes and obesity and the likelihood of having a child with autism or another developmental disability.

http://www.sciencedaily.com/releases/2012/04/120409103942.htm

Plus in diabetes, minor bouts of hypoglycemia have been shown to cause neurodegeneration resembling that seen in Alzheimers :

Brain atrophy linked with cognitive decline in diabetes

http://www.sciencedaily.com/releases/2013/09/130912093807.htm

Re ME/CFS - were you thinking of the study associating leptin with the level of fatigue?

 

[taniaaust1]

Possible, but I very much doubt it is about them or 'us carrying a genetic weaknes' - given the number of genetic studies all coming up empty (ie one would expect it to have been picked up by now). More likely imo that something is actively interfering with its function ...

I think there may be several genes involved in ME/CFS (maybe affecting methylation or maybe affecting immunity or combos of genes making us susceptable) and hence why just looking for one hasnt yet been easily found.

Faulty genes more easily allow something else to come along and knock something out.