Brain iron Deficiency Changes Adenosine receptor in Cortico-Striatum. Connection with RLS. 2022

[pattismith]

Brain Iron Deficiency Changes the Stoichiometry of Adenosine Receptor Subtypes in Cortico-Striatal Terminals: Implications for Restless Legs Syndrome​

Barcelona 2022

Abstract​

Brain iron deficiency (BID) constitutes a primary pathophysiological mechanism in restless legs syndrome (RLS).

BID in rodents has been widely used as an animal model of RLS, since it recapitulates key neurochemical changes reported in RLS patients and shows an RLS-like behavioral phenotype.

Previous studies with the BID-rodent model of RLS demonstrated increased sensitivity of cortical pyramidal cells to release glutamate from their striatal nerve terminals driving striatal circuits, a correlative finding of the cortical motor hyperexcitability of RLS patients.

It was also found that BID in rodents leads to changes in the adenosinergic system, a downregulation of the inhibitory adenosine A1 receptors (A1Rs) and upregulation of the excitatory adenosine A2A receptors (A2ARs).

It was then hypothesized, but not proven, that the BID-induced increased sensitivity of cortico-striatal glutamatergic terminals could be induced by a change in A1R/A2AR stoichiometry in favor of A2ARs.

Here, we used a newly developed FACS-based synaptometric analysis to compare the relative abundance on A1Rs and A2ARs in cortico-striatal and thalamo-striatal glutamatergic terminals (labeled with vesicular glutamate transporters VGLUT1 and VGLUT2, respectively) of control and BID rats.

It could be demonstrated that BID (determined by measuring transferrin receptor density in the brain) is associated with a selective decrease in the A1R/A2AR ratio in VGLUT1 positive-striatal terminals.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8911604/

 

[datadragon]

HI, I was posting a bit about that before. Brain iron deficiency produces increased sensitivity of the cortico-striatal terminals to release glutamate, Dr. Ferré had found that low levels of receptors of adenosine, a chemical in the brain that regulates neurochemicals, lead to abnormally high levels of glutamate and dopamine https://forums.phoenixrising.me/thr...g-apathy-social-withdrawal.90402/post-2450113 I also briefly was starting to look how the dopamine transporter (DAT) is regulated by Zinc which directly interacts with the protein. Zinc also is involved with ceruloplasmin that makes both our copper and iron bioavailable (usable). Zinc happens to be sequestered within the cell during inflammation and infection states induced by pro inflammatory cytokines by metallothionein, and its uptake/absorption is also reduced so I was considering that as more discussion of a starting point rather than iron possibly as the basis for many of these kind of inflammation linked symptoms. In addition, A2A receptor can suppress immune cells, thereby protecting tissue from inflammation https://pubmed.ncbi.nlm.nih.gov/11780065/
https://pubmed.ncbi.nlm.nih.gov/12565702/

Zinc deficiency potently decreases the activities of extracellular adenine-nucleotide-hydrolyzing ectoenzymes, delaying both extracellular ATP clearance and adenosine generation I had posted. https://forums.phoenixrising.me/threads/brain-adenosine-modulation.90819/post-2443941 Adenosine A3 receptors interestingly regulate serotonin transport via nitric oxide and cGMP also https://pubmed.ncbi.nlm.nih.gov/7525554/

 

[Violeta]

What is causing the iron deficiency in the brain?

Too bad they didn't measure zinc content, too.

Patty, do you have RLS? I used to have RLS really bad, and I've never heard anyone else say this, but at times it felt as though I had the feeling all over my body. It's not so bad anymore, and now when I get it I take some Butcher's broom and tyrosine and it clears up in about 15 minutes. Waiting for that to work is torture, though, when you're trying to go to sleep.

 

[Violeta]

It's weird that a symptom of Parkinson's is restless leg, but in Parkinson's there is iron overload in the brain.

Iron is found in high concentration in some areas of the brain, and increased iron in the substantia nigra is a feature of Parkinson's disease.

And also, there is this.

The basal ganglia — a brain circuit group that plays a role in Parkinson's disease (PD) symptoms — has adenosine A2A receptors located next to dopamine receptors, the target of many other Parkinson's medications.

I don't know, today is one of those days when I can't put 2 and 2 together. I think it's cause of pollen allergies.

 

[datadragon]

Iron is found in high concentration in some areas of the brain, and increased iron in the substantia nigra is a feature of Parkinson's disease. It's weird that a symptom of Parkinson's is restless leg, but in Parkinson's there is iron overload in the brain.

Individuals lacking ceruloplasmin display iron overload in selected tissues, including liver, brain, and retina. Here is just one of many. http://www.ncbi.nlm.nih.gov/pubmed/22515740 you can have plenty of copper intake but still be deficient at the same time (and iron) due to the lack of ceruloplasmin to make it usable. Most are not low in intake but low in being able to produce ceruloplasmin allowing both unbound copper and then iron to build up and have a potential deficiency at the same time. It has been explained that it is kind of like being in the middle of the ocean surrounded by water, yet still starved of usable water to drink. It seems that most here do not properly understand that ceruloplasmin requires Vitamin A, Zinc, and Magnesium and that the zinc and Vitamin A are affected by the inflammation and infection state which can cause the deficiency. It is actually one of the core issues with alzheimers by the way I had only briefly mentioned before a few times https://forums.phoenixrising.me/thr...lock-il-6-trans-signalling.90433/post-2438840

 

[pattismith]

What is causing the iron deficiency in the brain?

Too bad they didn't measure zinc content, too.

Patty, do you have RLS? I used to have RLS really bad, and I've never heard anyone else say this, but at times it felt as though I had the feeling all over my body. It's not so bad anymore, and now when I get it I take some Butcher's broom and tyrosine and it clears up in about 15 minutes. Waiting for that to work is torture, though, when you're trying to go to sleep.

I have moving legs yes, and sometimes I feel agitated inside.

But nothing that keep me from sleeping.

How is your ferritin level?

 

[Violeta]

.I have to seen if adenosine receptors and/or iron are involved in postherpetic neuralgia or shingles.

Shingles Iron Yes.... anemia seems to be common with shingles

I hope no one minds me putting some notes here that are incomplete thoughts. I am afraid if I have to move on to the dog or chores I might forget and then the thoughts will be gone forever.

lysine
egg white
avidin
lactoferrin
iron/stiff neck
iron/hair loss
biotin

 

[Violeta]

I have moving legs yes, and sometimes I feel agitated inside.

But nothing that keep me from sleeping.

How is your ferritin level?

That's good. I haven't had anything tested in a long long time.

 

[Violeta]

Individuals lacking ceruloplasmin display iron overload in selected tissues, including liver, brain, and retina. Here is just one of many. http://www.ncbi.nlm.nih.gov/pubmed/22515740 you can have plenty of copper intake but still be deficient at the same time (and iron) due to the lack of ceruloplasmin to make it usable. Most are not low in intake but low in being able to produce ceruloplasmin allowing both unbound copper and then iron to build up and have a potential deficiency at the same time. It has been explained that it is kind of like being in the middle of the ocean surrounded by water, yet still starved of usable water to drink. It seems that most here do not properly understand that ceruloplasmin requires Vitamin A, Zinc, and Magnesium and that the zinc and Vitamin A are affected by the inflammation and infection state which can cause the deficiency. It is actually one of the core issues with alzheimers by the way I had only briefly mentioned before a few times https://forums.phoenixrising.me/thr...lock-il-6-trans-signalling.90433/post-2438840

Raising ceruloplasmin can be difficult. I am working on the zinc, drinking lots of kefir which should supply a good amount of vitamin a, let me see if it supplies enough magnesium.

I see low ceruloplasmin can be caused by chronic liver disease, and a couple of other things.

 

[datadragon]

Raising ceruloplasmin can be difficult. I am working on the zinc, drinking lots of kefir which should supply a good amount of vitamin a, let me see if it supplies enough magnesium.

I see low ceruloplasmin can be caused by chronic liver disease, and a couple of other things.

The core issue would be when its caused from being in a high inflammation - infection state as that is going to lower the ability to make ceruloplasmin if prolonged as zinc and vitamin A will become less available to utilize. Zinc is also involved i n vitamin A metabolism and vice versa so if one is a problem the other will also be.

Shingles Iron Yes.... anemia seems to be common with shingles

From what I posted before, shingles is benefitted by the ACTIVE form of Vitamin D. Your doctor can prescribe calcitriol 1,25-dihydroxyvitamin D3 which is the active form which may be much more helpful during active shingles infection for example according to that research since the conversions to the active form can be problematic during that time even taking magnesium which is usually more of the issue when in a non inflammation state and also gets heavily lowered as well during high inflammation or infection. Unfortunately I then found even taking 1,25 sometimes doesnt do the job and thats because Zinc and Vitamin A are next needed for the Vitamin D receptor to function properly in its effects and those can also be lowered during chronic inflammation/infection so if even the 1,25 form isnt working great by itself in those special cases, those nutrients may be potentially added as well temporarily in low doses which is also pretty new information I've mentioned a few times. https://forums.phoenixrising.me/threads/dang-those-vitamin-d3-levels.91152/post-2449906 The zinc has been the common link among these problems which is why the focus has been on that especially considering all pro inflammatory cytokines induce metallothionein and sequester zinc within the cell. Obviously they have antivirals that may also help during those states.

I have moving legs yes, and sometimes I feel agitated inside.

Out of curiosity maybe a few boiron zincum metallicum 30c under the tongue when you have restless legs may possibly help in that state from my testing. There are many forms of zinc being looked at but most dont get absorbed well during inflammation or infection states orally which I havent yet explained well. Another possibility might be a drop or two or good state ionic zinc sulfate on the back of each hand Ive tried or under the tongue. Those may potentially help in the high inflammation state.

 

[Violeta]

The zinc has been the common link among these problems which is why the focus has been on that especially considering all pro inflammatory cytokines induce metallothionein and sequester zinc within the cell.

Yeah, this is what I was just thinking about. I have to work on that, too. I am going to get back on CBD consistently to work on it from that angle, and then make sure to get enough zinc, magnesium, Vitamin A, and Vitamin D. Thank you.