From an article I found about opiates and taupathies. Related to Alzheimers, but wondered about PSP...could codeine/opiates cause PSP? Could minocycline be useful-has anyone tried it? (see end of article)
Excerpt below (link to full article at end)
What are the recent advances?
The new discoveries relate to abnormal proteins within the dendritic spines and their heads. These are the tau proteins and the proteins of the post-synaptic density.
What are tau proteins and how were they abnormal?
The dendritic spines have scaffold-like structures called microtubules within them in order to maintain their shape. Tau proteins help stabilise the microtubules. Abnormal tau proteins result in an abnormal immune response and reduction in dendritic spine density (dendritis or dendropathy) in the hippocampus or memory centre (hippocampitis) and Alzheimer`s disease.
The recent discovery was by Dezhi Liao, Ph.D. Associate Professor , Department of Neuroscience University of Minnesota who has previously challenged the conventional model of opioid dependency using a dendritic spine model. ( Mu-opioid receptors modulate the stability of dendritic spines) Associate Professor Liao found that tau protein accumulated in dendritic spines and led to abnormal synapses. These changes occurred prior to nerve cell death in Alzheimer`s disease.
What is the post-synaptic density (PSD) and how was it abnormal?
The PSD is a circular disc with a central depression i.e. doughnut shaped, which lies in the head of the dendritic spine. The disc lies below the synapses. There are abnormal mutations of the proteins of the PSD in many psychiatric and neurological diseases. These mutations are associated with an abnormal immune response within the brain and reduction in dendritic spine density (dendritis or dendropathy).
Professor Seth Grant and colleagues isolated 1461 proteins from the PSD. Mutations of PSD proteins caused 133 neurological and psychiatric diseases.
Conclusion
These findings provide further evidence that most psychiatric and neurological diseases may relate to the model of
1. An abnormal immune response to an immunogen or auto-immunogen.
Dr Noble et al have used minocycline (an antibiotic) in mice with abnormal tau protein related Alzheimer`s disease. The minocycline was noted to reduce inflammatory markers which are elevated in Alzheimer`s disease. No mention was made of the effect on dendritic spinesor clinical features in the treated animals.
Minocycline has already been used in animals with fragile X syndrome and was noted to promote dendritic spine maturation perhaps by an anti-inflammatory action. Minocycline has been used in a small clinical trial in patients with fragile X syndrome with some success. Larger trials are awaited.
It is possible that suppression of the abnormal immune response to abnormal proteins may be important in the treatment of brain disease in the future.
Perhaps brain disease will soon be regarded as neuro-inflammatory rather than neuro-degenerative.
References
Characterization of the proteome, diseases and evolution of the human postsynaptic density
Alzheimer's: Tau Disrupts Neural Communication Prior to Neurodegeneration
Anti-inflammatory impact of minocycline in a mouse model of tauopathy
Minocycline promotes dendritic spine maturation and improves behavioural performance in the fragile X mouse model.
My mother never even took paracetamol and certainly never touched codeine. She was really anti taking unnecessary tablets. She did have high blood pressure her whole life though, which I think is implicated in brain diseases.
Hi Susan 789
I have very little knowledge of this area, but from my general reading I don't believe there is any evidence to link habitual opiate consumption with PSP. I think the data on Alzheimer's (tau) that you quote was mainly animal research. The article's quote "Perhaps brain disease will soon be regarded as neuro-inflammatory rather than neuro-degenerative" is interesting. However, other researchers (if I've understood correctly) have found that neuroinflammation (a hot subject) is itself a result of neurotoxicity, and thus neuroinflammation does NOT CAUSE, in itself, the death of neurons.
Here is one study:
Ann N Y Acad Sci. 2008 Oct;1139:318-30. doi: 10.1196/annals.1432.032.
Defining "neuroinflammation".
O'Callaghan JP, Sriram K, Miller DB
Source ...Centers for Disease Control and Prevention-NIOSH Morgantown, West Virginia, USA. jdo5@cdc.gov
(a quote from this paper "neurotoxicity appears to be the cause rather than the consequence of proinflammatory signals).
There are psychiatric conditions related to opiate abuse. However, the suggestions for the " initiating cause" of PSP (and other tauopathies and synucleinopathies etc) have been viruses, toxins, drugs, cellular free radical damage and genetics. Yet there is little to suggest the influence of opiates or those "inflammatory processes" in the brain having any connection to PSP or similar conditions.
Thanks, looking for history, I know one psp person who had prolonged exposure to codeine long before the psp. I also caught threads of discussion during my research where at least 2 others had mentioned chrontic pain in the years prior to psp onset and use of T3's and other non-prescription codeine to control. This kind of use of codeine and other opiates would not show up on medical records, as it may not be something that is reported by patients especially if they have been taking them without prescription, as they are available in Canada. Nothing in the questions asked by our neurologist asked about it either.
Simple thoughts
There is a link between opiate dependency and abnormal tau proteins, the abnormal tau proteins are linked to the neuro degenerative diseases. Dependency is not the same as addiction--it could be a very low dose habitual use, not talking about excessive abuse or addiction. Just regular long term dose of the drugs. The reality of this PSP disease as I see it, is that it is so rare and not well studied that Dr's pronounce their death sentence on our loved ones, and shrug, and say, no one knows, get your affairs in order, prepare for misery in the later stages, and come back every 6 months or so until you are dead. Since they are not taking complete lifetime histories, we may never know what the cause is, unless we, the people suffering start asking questions and find out what we have in common. There are causes, likely multiple, but somewhere if we all start asking what we have in common, we may find something, at least one cause. Cause is a starting point.
Mum has CBD not PSP so I don't know how much her history of medication will help you but it may sound familiar to others with CBD. She has high blood pressure. Never taken codeine, been taking paracetamol for years and took steroids for years for Polymyalgia rheumatica. She suffered pain, stiffness and inflammation in the muscle around the neck and shoulders for years. I mentioned this to the neurologist when she was diagnosed with CBD but he didn't seem to think it was important. Good luck with your research, keep looking.
Thanks for your reply, I think I am going to start a database of lists for each psp ID, if you think of any more things that you have wondered might have caused this, symptoms that seem unrelated etc in your mom, things like daughter_julie listed, please let me know. It doesn't take much to create lists and compare them, maybe we find something that is in common, something that is overlooked, like inflammation in neck muscles or who knows.
Sorry, can't think of other things that could be relevant, up until her 70s she was very healthy and took no medication, she's 88 now. Other people on the site have wondered if grief could be a factor, I understand that people can have the disease 20 years before symptoms start, I've thought back to what happened in her life 20 years ago and can only come up with the death of my father 19 years ago. When mum was diagnosed she was asked to participate in research being carried out by a professor at the hospital, she agreed and samples were taken. He is researching whether PSP/CBD is genetic. Mum was asked if she would like to be sent a copy of the results, no idea how long we will have to wait, it goes without saying I will post on the site if he finds anything of interest. She did work on a farm during the war (land army) ? pesticides, unlikely to be a cause due to the length of time.
My mom also lost a very good friend and it hurt her terribly, I also wondered if this might be a trigger for the disease. I am not ruling out pesticides, even over a long period of time, as with the study on opiate dependency, the damage can be done many years previous. Maybe it is something that many people have as a result of exposure to something, but is only triggered in a few people later in their lives by another event. Mom is also in a study, but they don't ask any of these kind of questions, they are more about what mom feels and thinks now, very little detail about history.
I totally agree Susan. I guess these things (doing surveys) cost money, something PSP doesn't seem to have much of given its rareness. It would be super tough to structure a questionnaire around all aspects of life too. I mean, where would you begin? For all we know it might be related to Psp sufferers mothers habits when the patient was in the womb! Don't get me wrong, I'm not dismissing it, I think more should be done, but gosh it would be a really difficult survey to write! My skewed and entirely unfounded thoughts have ranged from the amalgam fillings in my dads mouth (he was a teeth grinder) perhaps little bits of mercury slowly filtered to his brain over many years? the blood pressure medication he was given when Psp began, statins, chemical use over the years ( dad loved a bit of bleach!) it could even be related to the metal in the water pipes... It would be lovely to know what has been the cause of this dreadful disease, that way we could never let it happen to anyone else ever again. I wonder if the future holds a wonderful new science that might help us pinpoint the exact cause.
I think that is where we start--we all have lists of things we think might have caused this disease. What if we all posted those lists? That's how I started this. I originally started with Lyme and tick borne illnesses that fit the symptoms, and then started moving through other things. I am not a Dr, but I am a data analyst, one of the things that I have done for years is take a ton of data--lists--and look for commonalities. I take the lists, clean the data into uniform structures (ie spelling, meaning etc) and then look for links running queries on that data. I don't think that is too difficult and we can keep adding things to each list for each userID until we have datasets. The fillings were on my list too. I just added high blood pressure. I had thought about pesticides--and was starting to compile a list of those used on the farm--maybe others use them in gardens? I don't know of any other site that has such a concentration of PSP people and any better opportunity to collect info on this very rare disease. We know the Dr's aren't doing it, but maybe we can.
The only thing I would say about codeine is that it makes one constipated, my husband has far too much difficulty with that now, so we stay well away from codeine.
In another life, he would never have so much as an aspirin whatever pain he was in.
Can I asks separate question about food? My husband eats a varied and good diet and on the whole copes very well, he has cereal, usually, oatmeal made tou
"baby constituency " for
breakfast, lunch is always a soft boiled egg and toast, main meal whatever I cook, cut small though. But for sometime now he chokes very badly on his breakfast and I'm wondering if it's because of the secretions on his chest first thing in the morning. Should I switch things around a bit, or leave his breakfast till later in the morning?
Any thoughts, suggestions would be very much appreciated.
Replying to Dorothy re food: Could be time for another SALT appointment/review as it could just be the consistence of his food that is no longer appropriate? (I'm writing from the UK- I didn't know before Mum's illness that a Speech and Language Therapist could be called in by the Care Home to assess her swallowing.)
Susan: don't know about the drugs but my mother certainly had high blood pressure: she nearly died from heart failure a few years before the PSP was diagnosed. She would have been on medication for that, medication for IBS/ diverticulitis and had also had cancer a couple of times....
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