Dysautonomia subgroup in PD

[aspergerian]

Is the following a dichotomy or nearly so?

PwP whose PD is significantly biased by dysautonomic pathologies?

PwP whose PD is not significantly biased by dysautonomic pathologies?

[ElliotGreen]

If you look in my recent responses you'll see a brief summary of Janice Walton-Hadlock's ideas on PD and the autonomic nervous system. Basically, JWH would say that almost everyone with PD has a problem with being pathologically stuck in a certain autonomic nervous system mode.

healthunlocked.com/parkinso...

As far as conventional medicine, I do recall reading that there can be different pathways through the brain in terms of alpha-synuclein clumping and neurodegeneration. Some people have their autonomic nervous system affected by neurodegeneration earlier (perhaps preceding the conventional motor symptoms of PD???), and some people have their autonomic nervous system affected much later.

Basically, I think the distinction you are making is valid.

For example, I am fortunate in that I do not (as yet) have constipation as one of my symptoms of PD. Constipation can result from problems with the autonomic nervous system.

parkinson.org/pd-library/fa...

[rescuema in reply to ElliotGreen]

Constipation is also a symptom of serotonin deficiency (or potassium, b12, zinc, magnesium, etc), which also contributes to depression and anxiety. Pathogenesis of a disease differ for everyone, especially in PD, often referred to as a "snowflake disease."

[ElliotGreen in reply to rescuema]

I edited my reply to say that, "Constipation can result from problems with the autonomic nervous system."

Because, as you mention, there can obviously be other causes. It can be related to medication, and diet, too. Or just not drinking enough water.

[rescuema in reply to ElliotGreen]

Also to be noted -

"increases in dopamine cause oxidative stress and damage serotonin neurons. Similarly, chronic l-dopa produces deficits in serotonin neurotransmission, including decreases in both serotonin cell bodies within the dorsal raphe and serotonin neurotransmitter concentrations in several forebrain regions. Since serotonin is involved in many important physiological processes including mood and cognition, l-dopa induced serotonin deficits may play a role in the side-effect symptoms observed in Parkinson’s disease patients treated with l-dopa."

ncbi.nlm.nih.gov/pmc/articl...

So even if one starts out PD without serotonin deficit, 5-HT deficit related impairment and 3-OMD metabolite induced oxidative DNA damage are likely consequences of l-dopa therapy with slow progression to further dysautonomia.

[ElliotGreen in reply to rescuema]

"Direct evidence will be provided that increases in dopamine cause oxidative stress and damage serotonin neurons."

Now THAT is evidence contrary to levodopa being neuroprotective.

[rescuema in reply to ElliotGreen]

I don't think anyone can claim outright that l-dopa is neuroprotective. However, you do have to take account of l-dopa allowing one freedom of movement and physical exercise, which WILL contribute to slowing the progression and countering oxidative stress.

[Lana666 in reply to rescuema]

Rescuema, I Should’ve read your comment about exercise before posting a question. Of course exercises, that’s clear. Still, anything else?

[Lana666 in reply to rescuema]

Rescuema,

Very “encouraging “ first sentence:(. I knew about PD progression leading to serotonin production depletion - even “better” : the disease and a drug work synergetic. Lovely.

Any word of wisdom from you, how to protect/boost serotonin, without antidepressants?

[rescuema in reply to Lana666]

Sorry it can't be more encouraging but generally you tend to eventually pay for using any pharmacologic substance that isn't natural/balancing to the body. Researchers are advancing in the knowledge in the field and finally making notable advances by investigating genomics and methylation - a word that until very recently been frequently mocked as hackery. I find the research such as the below promising, and hopefully we could find a way to prolong the efficacy of useful therapeutics and taper the devastating side effects soon.

ncbi.nlm.nih.gov/pmc/articl...

In the meanwhile, the best possible thing you could do for yourself is to eat well (lower inflammation), exercise or move around as much as possible, which helps with serotonin production.

startstanding.org/sitting-n...

healthline.com/health/how-t...

[Lana666 in reply to rescuema]

Thank you

[Oceanflow in reply to rescuema]

Some serotonin neurons can secrete dopamine under certain circumstances ... ...how does that fit in to the puzzle...

[rescuema in reply to Oceanflow]

"This is the first direct evidence of dopaminergic neurotransmission in DRN neurons and its modulation with rAAV-D2Rs gene therapy confirms the serotonin hypothesis in LID, demonstrating that regulation of serotonergic neurons achieved with a gene therapy approach offers a novel and potent antidyskinetic therapy...In conclusion, the current study shows that DA release from DRN 5-HT neurons can be regulated with ectopic expression of D2Rs, altering the activity and DA release properties of these neurons in a therapeutically meaningful way. These data add important evidence to the current understanding of LID and serve as to confirm the serotonin hypothesis in LID, showing that directly regulating serotonin neuron activity can inhibit LID development."

actaneurocomms.biomedcentra...

However, I believe it's important to trying seeing the whole picture - whether a body is pushed to a certain imbalance and epigenetic event due to oxidative stress, compensatory mechanisms, methylation imbalance, or nutritional deficiency that also blocks transsulfuration pathway allowing detox and contributes and cycles back to further toxic oxidative damage to thwart additional cell viability and functions. When one mechanism loses a balance, it basically creates a domino effect further down the chain. When serotonergic neurons contribute to levodopa-induced dyskinesia, it may be partially in result of methyl donor depletion. L-dopa may also contribute to cell dysfunctions/death through competitive inhibition/blocked mechanism under finite resources.