Parkinson cause could show new gut connection.

Discussion in 'Other Research' started by Tim Foley, Jun 27, 2019.

  1. Tim Foley

    Tim Foley Member

    ABOVE: Scans of the brains of mice show a reduction in dopamine (colored areas) in the striatum of the Parkinson’s disease model that was injected with pathogenic α-synuclein (right; control mouse on left).
    TED DAWSON ET AL. / NEURON, 2019
    I​
    n 2003, Heiko Braak, then a neuroanatomist at the University of Frankfurt, suggested that Parkinson’s disease pathology may start in the gut and travel from there to the brain long before a patient shows symptoms. The idea, based on postmortem analyses of samples from parkinson’s patients, has been hotly debated ever since.
    In a study published today (June 26) in Neuron, Ted Dawson, a neurologist at Johns Hopkins School of Medicine, and his team created an animal model of the disease by injecting particular proteins into the stomachs of mice. About a month later, the animals showed symptoms of Parkinson’s disease. The model not only demonstrates how the disease protein can travel up from the gut to the brain, but also presents nonmotor symptoms rarely seen in other animal models.
    The Scientist spoke with Dawson about the work.
    [​IMG]
    Ted Dawson
    JOHNS HOPKINS MEDICINE
    The Scientist: Why did you develop this model?
    Ted Dawson: Well, there is this idea that was building that was started by Dr. Braak that Parkinson’s disease could start in the gastrointestinal tract, and there was good human data that suggested that possibility. What was lacking was an animal model that could validate that hypothesis. [The model] validates [the hypothesis] by providing evidence that it’s possible that Parkinson’s disease could start in the gut.
    There’s been this very detailed study by Dr. Braak and later by other pathologists that the pathologic alpha-synuclein seemed to progress from the gut up the neuroaxis into the brain, and what our work shows is that this is possible.
    See “Can the Flu and Other Viruses Cause Neurodegeneration?

    TS: How did you do it?
    TD: We took pathologic alpha-synuclein, . . . and then we injected those preformed fibrils into the pylorus [an area of the stomach close to the small intestine] into one of the mice near where the vagal nerve innervates those regions. Over time, the animals developed Parkinson’s disease.
    [To clarify], we’re injecting exogenous pathologic alpha-synuclein. And that is causing the endogenous synuclein to misfold and transmit up the vagal nerve. We know that because when we injected the exogenous alpha-synuclein in the alpha-synuclein knock-out, nothing happened. So the exogenous alpha-synuclein is not the synuclein that’s transmitting. It’s causing the endogenous synuclein to misfold and transmit.
    TS: What is the importance of the vagus nerve in the pathologic process?
    TD: It’s essential for the pathologic alpha-synuclein to get up to the brain. In a subgroup of animals, we performed vagotomies and the pathologic alpha-synuclein did not ascend into the brain. And as a consequence of that, the animals did not develop Parkinson’s disease.
    TS: What else makes this model unique?
    TD: One of the other things that we think is really exciting about this model is that not only do the mice have the motor features of Parkinson’s disease, they also have the nonmotor features. They’ve got cognitive dysfunction, anxiety, depression, problems with smell. And so we now have an animal model to study those problems. We hope that it opens up a whole new set of investigations using those animal models.
    This model shows that it’s possible for synuclein to ascend from the stomach via the vagal nerve to the brain. What we don’t know in humans with Parkinson’s disease is how that process starts. That would be the next step, to figure out how it actually starts in humans.
    S. Kim et al., “Transneuronal propagation of pathologic α-synuclein from the gut to the brain models Parkinson’s disease,” Neuron, doi:10.1016/j.neuron.2019.05.035, 2019.

    https://www.the-scientist.com/news-opinion/mouse-model-shows-how-parkinsons-disease-begins-in-the-gut-66048
     
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  2. Not dead yet!

    Not dead yet! Well-Known Member

    A family member sent me this too. It's really interesting. I was wondering if the protein/ prion is absorbed from the gut or how does it get there? And the answer seems to be that the nerves in the gut are damaged first and then the disease travels up the vagus nerve to the brain. Once there, it's officially Parkinson's. https://onlinelibrary.wiley.com/doi/abs/10.1002/mds.23838

    I wonder if people can feel the dysfunction but it's not "clinically significant." Oh how I ate that phrase.

    I also wonder if we can find out what causes the damage in the first place.
     
  3. Aidan Walsh

    Aidan Walsh Well-Known Member

    Why are some now diagnosed with CFS for years now told they have Parkinson's I have heard this now over the years in numerous? Could Parkinson's be CFS all along then it gets worse in time?
     
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  4. Merida

    Merida Well-Known Member

    Hi Aidan - met you on Open Medicine. I have many Parkinson symptoms : tremor on right side, jaw tremor, dysautonomia, restless legs, serious fatigue, visual changes, more. And some people did well on Mirapex. My Mom had them too, but they did not progress - she lived to 95 but suffered terribly last 10 years.

    Thought a lot about this- have always suspected I have a dopamine issue. Wellbutrin helped tremendously for 5-6 years - and it is a weak agonist of serotonin, norepinephrine, and dopamine. Opiates also helped tremendously - Pain, of course, but an important beneficial side effect was some significant help with fatigue. Suspect the opiate boosted dopamine.

    My problems started after a neck/ pelvis injury. Think structure is important - and dopamine production may relate to that. But also I have a long, redundant colon that can kink and twist.

    Just don’t know about this yet.
     
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  5. Aidan Walsh

    Aidan Walsh Well-Known Member

    thanks Merida, yes I am glad you responded to the medicine I also wonder what is your true diagnosis it may have been Parkinsons all along & not CFS I think a lot are given this CFS label or it could be all the same illness & some

    progress to Parkinsons. Are you going to try to see if it is possible that you may have a GSD type Glycogen Storage Disease? I think you should ask to be screened & demand the Doctors do the full proper tests. Wish you wellness hugs & thanks
     
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  6. Aidan Walsh

    Aidan Walsh Well-Known Member

    Also I am seeing some getting diagnosed with Eagle Syndrome with proper CT Contrast Scans & experienced skull based Surgeons doing the operations, the ones with success are have full removals not partial ones of the calcified Bones...I had an issue injury right abdomen in Boxing took a very bad blow

    there I think Vagus Nerve damage as a possibility or the impact caused spinal fluid leaks from the pressure of the blow. I still feel the pain right side abdomen to this day it never lifts. Its not my Appendix, that was already removed decades before bit is the same area I got hit. It was by far the hardest blow I ever got in

    Boxing over the years I was ill weeks later my illness started :)
     
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  7. Merida

    Merida Well-Known Member

    Aiden, I did not know that you were a boxer. Yes, I can imagine that you may have serious pelvis, spinal, neck misalignments? I can share my experience - I was healthy, fine, no pain until I went ( first ever) to a chiropractor for a sore popping hip from yoga class . I was 49. He twisted and jerked my neck and pelvis, and that started everything. I was bed ridden one year.

    I also had terrible right sided abdominal pain - not appendix. Think my colon was twisted. Still have significant issues with that, but not much pain now. A torqued pelvis can cause huge problems - and it can pull the neck out. Appreciate that the spinal cord is attached inside the sacrum at S2, and all the branches from the end of the spinal cord ( ie cauda equina) go through the holes in the sacrum to the lower abdomen, legs.

    But having said that, I have certain things that may make me more susceptible to alignment problems : probable Ehlers Danlos, mild scoliosis, small skull base ( measured by neurosurgeon), hypodevelopment of sacrum ( small holes), Long, redundant colon ( a malrotation? ), and more structural things. So what genetic issue caused all this structural stuff ? Glycogen storage disorder or connective tissue disorder or ? I also think I may have a not so perfect blood brain barrier, which may predispose to chronic Lyme etc ? My lactate dehydrogenase was measured 5-6 times - always 60-70% of normal. Enzyme deficiencies are certain genetic. And LDH deficiency is glycogen storage disease #11. So, I just don’t know yet.

    Have you tried a traditional osteopath ? They may have some important insight.
     
  8. Aidan Walsh

    Aidan Walsh Well-Known Member

    thanks, Merida, have you been tested yet for the GSD types? Not sure if I have those things you mentioned above from Boxing but I now believe Eagle Syndrome is likely but I still do not know if other things going on now. I have to wear a 24-hour blood pressure machine to record if I have high blood pressure but doubt I do I know I got Syncope,

    diastolic dysfunction even now LVP Left Ventricular Hypertrophy but I searched in Published Papers LVP can come with Eagle Syndrome also so can Diastolic dysfunction & Syncope as well. I am on Facebook in Southampton UK under Aidan Walsh the Gold Angel is my profile pic. thanks all the best are you well yet? I have a nephew recently twice had

    Lymphoma, odd things going on in my Family now one nephew Died last year within one year being sick maybe vascular issue no one knows. Not tried osteopaths I saw natural Docs years ago no help at all so stopped going to them entirely spent lots of money for nothing
     
  9. Aidan Walsh

    Aidan Walsh Well-Known Member

    Merida, I also have EDS they now say not EDS3 but HSD but still think they may be wrong it could be something else even HATS or even Alpha-Gal Meat Allergy I will be tested for both soon AG & Hereditary Alpha Tryptasemia Syndrome. I am still waiting to be tested for GSD Panel I am looking for a Private lab in Europe

    now or London area. They told me in London I had partial Marfans but recent Genetic Doctor said No but my brother has the sunken chest found in Marfan's Syndrome mine is slightly but not much. I have the 2 test kits here for AG & HATS this one is a moth DNA swab to mail back to Houston Texas cost is $169.00 only at

    key in tryptase the test will open up on Home page there they sent it here by mail you need a Doctor to sign for the test to send back to them an MD is fine. site here Houston Texas www.genebygene.com I no doubts have copies of tryptase my tryptase blood here is 10 anything above 8 is highly likely HATS...
     
    Last edited: Jul 24, 2019
    Merida likes this.
  10. Merida

    Merida Well-Known Member

    Aidan, oh how I admire your search for answers. Yes, I think the connective tissue part may be very important. I did not suspect that this could be the genetic issue in my family until I wrote to a researcher expert in connective tissue / high intracranial pressure in Belgium. I listed the many family anomalies in structure. He kindly wrote back and and said he thought that the family members had EDS. But I never remember having hypermobility as an issue. So, I expect there are connective tissue differences yet to be described.

    And why may this be so important ? The entire lining of the CNS is connective tissue. So, blood- brain barrier and stability of the pelvis and upper cervical areas ( so important ! ) depend on the connective tissue that comprises the dural meningeal system. Of course the blood vessel construction is another issue - and also critical.

    Another interesting point : the author of Bitten : The Secret History of Lyme Disease and Biological Weapons ( Kris Newby) interviewed Dr. Burgdorfer prior to his death. He died from Parkinson’s. She asked him if he thought it was a Borrelia infection ( Lyme disease) that caused his Parkinson’s. He said to “ask the doctors.” Hmmmm.

    I have your email that you kindly gave me. Will write soon. Hard for me sit at my main computer to do that.
     
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  11. Aidan Walsh

    Aidan Walsh Well-Known Member

    Merida, Some do say Bartonella but Dr. Ron Davis says it is not being found, only theories also he is looking at East African Sleeping Sickness in the RNA it is Not in the DNA he has already searched. They just Published on IDO-1

    mutation they found he say Metabolic Trap...I was bitten & scratched by a Cat just before I got Sick but it is not supposed to become a chronic condition the immune system clears it even without any Antibiotics so I doubt I have Bartonella Hype bullshit going around it is EDS Complications 100% certain...
     
    Merida likes this.
  12. Aidan Walsh

    Aidan Walsh Well-Known Member

    Parkinson's is coming up in some even now at the NIH Study going on in ME/CFS
     
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  13. Merida

    Merida Well-Known Member

    Hmmm. You were bitten / scratched by a cat. The organism commonly associated with “cat scratch fever” is Pasteurella multocida - which I actually isolated on several occasions in the clinical lab. But this organism was very sensitive to antibiotics ( in the 1970s). However, it can produce meningitis and other complications. Will email more.
     
  14. Aidan Walsh

    Aidan Walsh Well-Known Member

    I had Meningitis Miami Neurology Emergency LP opening pressure was 500+ after it shot across the room it settled to 370 he gave me 80 mg of Prednisone but never recovered...He said highest pressure he ever saw Neurologist of 30 years he said I do not know how you are Alive...I wonder if the Eagle Syndrome which I now show on Dental

    Panoramic x-ray is causing the high pressure in spine as well I respond to only 3 medicines Doxycycline, Prednisone & Cortef he said my Normal read MRI I brought from Montreal General Hospital was Not Normal he said meniges with enlarged ventricles he said he knew then I have IIH he even suggested Pseudo Tumour Cerebri in the diagnosis back

    then...I know one Doctor who fully recovered from CFS 80 mg. of Prednisone, 50,000 i.u. of Vitamin D3 & OsCal Calcium daily he called this illness a 'snarled communication between the Brain & the Immune System', his Brain Spect Scan normalized I also respond to Hormone Vitamin D3 its like a Miracle when I am really bad but mine went too high

    at 900 so I stopped I took too much...My Brain Spect Scan in Montreal showed decrease uptake left temporal & parietal lobes & basal ganglia...I sometimes wonder if the basal ganglia could have to do with B vitamin Genetic thiamine & biotin 'Basal Ganglia Biotin Thiamine Deficiency Disease' I have not been tested...Dr. Ron Davis just Published last week his Team on IDO-1 mutation he said issues with

    Serotonin & some other issue he put out a YouTube Video from London few weeks back explaining the Metabolic Trap with IDO-1...I heard also GSD types could also be involved as well Alabama Genetics 2 out of 10 had rare type GSD 13 one had Parkinsons all along NIH also found one with CFS misdiagnosed he had Parkinsons as well, another

    had Major Depression not CFS...Bartonella 'cat scratch fever'???
     
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  15. Issie

    Issie Well-Known Member

    Interesting discussion here. My first wrong DX was Parkinson and then it was Multiple System Atrophy. Both wrong. And I have too high estrogen despite having had a complete hysterectomy at age 36. I have asked many men on both POTS and CFS forums if they knew if there estrogen was too high or if the balance between estrogen and testosterone was off. I have thought for years there was a connection with estrogen. Couldn't sort how it played into the picture. But my father having had prostate cancer, I often thought had I not had the complete hysterectomy, I may have gotten cancer. I did have endometriosis and that is a too high estrogen state.

    My also having Ehlers Danlos and there being connective tissue disorders definitely plays a part.

    I had a doc tell me to he careful what meats I ate. They pump them so full of hormones or feed them soy. All increases estrogen in them and when you eat, higher estrogen with you.

    I still have tremors and muscle issues and gait problems. But so far it doesnt really look like Parkinson and taking the meds for that made me so much worse. That DX was over 15 years ago. And I'm still alive and going.

    Issie
     
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  16. Aidan Walsh

    Aidan Walsh Well-Known Member

    Issie, Wish you answers & wellness soon have you looked into the GSD panel & what about iron overload? God bless you
     
    Merida likes this.
  17. Issie

    Issie Well-Known Member

    Not been checked for GSD. Am a carrier for hemochromatosis, but dont have it.

    @Merida , I did Terrible with upping my dopamine with Sinemit and SNRI. Made me much worse. But like you opitate medicine seemed to make a difference. My best medicine for my POTS and CFS/FMS is Tramadol and Bentyl. I cycle on and off and stay very low on them. Tramadol however works on all the neurotransmitters. So not sure if it's the combination or which factor that helps so much.
    Back in a flare now. Doc thinks its possibly CIRS or Lyme or the fungus that was found in my blood and organs that is gotten from mosquitos. So back to diet, detox and lots of herbals.

    Thanks @Aidan. I hope we all find our "purple bandaid".

    Issie
     
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  18. Aidan Walsh

    Aidan Walsh Well-Known Member

    thanks Issie, all the best wishes Aidan
     
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  19. Merida

    Merida Well-Known Member

    @Aidan Walsh and @Issie
    Hope you two aren’t too exhausted to continue this. You both amaze me with your experiences and the depth of your thinking and exploration. Thank you for sharing.
    Aiden, started long email, then got exhausted. Issie, I was on pure oxycodone for pain,nand I really think it was ( in addition to stopping pain) indirectly boosting dopamine - D2 receptor ? As I got energy too, and felt more normal. ( had spent 7 months with no pain meds - developed hyperalgesia/ allodynia - the opiates stopped this) Now I am switched to Norco - getting sick on it, and increased fatigue. Doesn’t matter to anyone but me. Oxycodone for chronic conditions is now forbidden by DEA.

    Okay - so what is the common denominator here? What is it that we all share? I am beginning to think that it is, indeed, a connective tissue difference - which results in blood brain barrier differences ( due to differences in the dura meningeal structure) and inherent instability in the pelvis, spine, neck. Aiden, your spect scan showed issues in your left brain areas? My brain MRI actually shows a smaller, squeezed up space in the left lower brain - related to how the dura is positioned. Neuro surgeon measured small posterior fossa. A person with a normal sized posterior fossa might be okay with some twisting of the dura in the brain, but not me.

    I learned from the osteopaths ( and sacro Occipital chiropractors) how the nervous system functions : there is a minute rhythm between the cranial bones ( especially occiput) and sacrum that pumps spinal fluid from the sacral bulb back to the brain against gravity. All the cranial bones have a specific minute motion that is critical to CNS function. The jaw is also involved ( just watch a few videos on You Tube by Dr. Brendan Stack. ) So people who have unbalanced, asymmetric sacrum/ pelvis, spine,etc. can have issues with pressures and circulation.
    So much to this - will try to post a photo of the sAcro Occipital findings.

    Now in my family and me there are lots of physical, structural differences: Spina bifida occulta,small holes in the sacrum( sacrum hypodevelopment), maxilla hypodevelopment ( teeth roots in sinuses),
    Heart structural differences, possible kidney differences ( on my left side), one side of face slightly smaller ( not very noticeable), cervical ribs, suspect pelvis differences, long rendundant colon, torque in index and little fingers, huge bunions/ hammer toes, Scoliosis, more.

    So what has caused all these things - could it be a glycogen storage disorder ? Or metabolic difference ? I call it the gift and the curse, as so many in the maternal have gifts. Will try to post photos I’d sacro Occipital brochure to show this asymmetry I mention.
     
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  20. Merida

    Merida Well-Known Member

    Hope you can see the asymmetry I mentioned, and check the impact of a sacrum that is unstable. Note that the jaw is also involved. The pictures are exaggerations of the asymmetries for demonstration purposes. I first saw this and thought it was ridiculous - 15 years ago. But, yep, that’s me.
     

    Attached Files:

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