1: Rev Neurosci. 2008;19(4-5):245-316.

Parkinson's disease as a neuroendocrine disorder of circadian function:
dopamine-melatonin imbalance and the visual system in the genesis and progression
of the degenerative process.

Willis GL.

The Bronowski Institute of Behavioural Neuroscience, Neurosciences Section,
Coliban Medical Centre, Kyneton, Victoria, Australia. gwillbro@bigpond.com

For more than 50 years, Parkinson's disease (PD) has been conceptualized as a
product of nigro-striatal dopamine (NSD) system degeneration. In spite of a
growing body of evidence depicting the mammalian brain as an interrelated
complexity of circuitous systems, dopamine (DA) deficiency of the NSD is still
regarded as the main problem, with DA replacement being the purpose of
therapeutic intervention. For at least 191 years circadian involvement in various
aspects of PD, including depression and insomnia, has been recognized as an
integral part of the symptom matrix of PD and yet attempts to elucidate the
involvement of this system is uncharted territory. The present review attempts a
major reorganization of mammalian brain into a coordinated complex involving the
NSD and the retinal hypothalamic tract (RHT) as the primary systems involved in
the retino-diencephalic/mesencephalic-pineal (RDMP) axis. Secondary systems
including the lateral hypothalamus (LH), the area postraema (AP) and the
subthalamic nucleus (STN) also form an integral part of this system as they have
been shown to be either intimately related to the primary systems of the RDMP
axis or have been shown to be significantly involved in the expression and
treatment of PD. A large volume of evidence suggests that the RDMP axis is
activated during the course of PD and during therapeutic intervention. Four types
of neurotoxicity associated with melatonin are identified and the susceptibility
of various parts of the RDMP axis to undergo neuropathological change, the
tendency for melatonin to induce PD-like behavioural toxicity, and the
relationship of this to PD symptomotology are described. This includes adverse
effects of melatonin on motor function, hypotension, the adjuvant use of
benzodiazepines, depression, insomnia, body weight regulation and various
biochemical effects of melatonin administration: all problems currently facing
the proposal to introduce melatonin as an adjuvant. It is suggested further that
traditional DA replacement may well work by exerting its effect upon the
circadian system, rather than simply replacing deficient DA. Activation of the
circadian function by antagonizing melatonin with bright light not only has
therapeutic value in treating the primary symptoms of PD but it shares a common
mechanism with L-dopa in reducing the occurrence of seborrheic dermatitis.
Concepts at the centre of understanding pineal function in PD, including pineal
calcification, melatonin deficiency, symptomatic versus protective features of
melatonin and antioxidative effects, are explained in a counterintuitive context.
Intriguing propositions including the role of the retina in the aetiology of PD
and that the nigra functions as a retina in this disorder are presented with the
intention to provide a new understanding of the underlying compromised function
in PD and to provide new treatment strategies. For the first time, abundant
evidence is presented describing PD as an endocrine disorder of melatonin
hyperplasia. The role of circadian interventive therapies and internal
desynchrony in the aetiology and progression of PD provides a new direction for
understanding the underlying physiology of a disease which is currently in a
state of impasse and provides new hope for those who suffer from its debilitating
effects.


PMID: 19145986 [PubMed - in process]

Rick - this makes a lot of sense to me. It is much closer to my own experience with PD.

Thanks!

Juan told me - several times - of a study done in Mexico - maybe a couple of decades ago? - in which massive amounts of melatonin were given to PD patients who then showed remarkable improvements in symptoms.

Maybe you can locate that information?

I, for one, am more than ready for a new line of therapeutic intervention.

rick, What exactly is melatonin and what is it's function in lay terms....thank u so much sir..

paula

But it is heartening to see neuroendocrinology having some bold input.

The way that I read it, melatonin is actually a problem in PD and should be avoided. There had been hints of this for years. An early therapy for PD was sleep deprivation which lowered melatonin production.

I become more and more convinced that the endocrine system is the Big Dog here and not the nervous. The latter has a very limited number of factors to account for a large number of symptoms. "OK, ya got dopamine. What else?"

The endocrine system, however, has hormone squirting out of everything but the ears. Cortisol, epinephrine, insulin, estrogen, testosterone, and a half-dozen more. And every one of them has receptors in the brain. You can explain a lot of non-motor symptoms with that kind of toolkit.

The heartening thing to me is that with a rich, complex collection of causes there are a rich, complex set of opportunities to intervene.

"The heartening thing to me is that with a rich, complex collection of causes there are a rich, complex set of opportunities to intervene. " ~ reverett123

Thanks Rick.

"The heartening thing to me is that with a rich, complex collection of causes there are a rich, complex set of opportunities to intervene. "

its true, but it is also a problem when you dont know what you are looking for. Current description of PD seems similar to ten blind men describing an elephant they are touching, each has a part of the elephant but no one has a complete picture (this is an Indian story, there must be an equivalent one here!).

girija

I takt melatonin mainly to help in sleeping .. now Rick raises doubts about the wisdom of it !
The article he presented is technically beyond me but on google I found a lot of articles which say that melatonin is good fo PD .
Example :
Jefferson Researchers Show Melatonin’s Potential Benefits In Preventing Parkinson's Damage
ScienceDaily (Oct. 25, 1999) — Melatonin could be a key to someday understanding how to treat Parkinson’s disease. Scientists at Jefferson Medical College have shown in the laboratory and in test animals that melatonin is effective in preventing a particular type of brain cell damage similar to that found in Parkinson’s.

MONTMORENCY CHERRIES CONTAIN MELATONIN -natural sleep aid
the cicadian rythmn is highly important because of R.E.M. sleep
this deep sleep repairs the brain ---this my own wording from all 16 years of research - from my natural approach to regain health
*no link to my brain"
however;
an article found here:

Cherries Found to Be a Natural Sleep Aid
by Jo Hartley, citizen journalist
See all articles by this author
Email this author


(NaturalNews) There is a tart cherry called Montmorency that contains a significant level of melatonin and hence is helpful as a natural sleep aid. The University Of Texas Health Science Center in San Antonio recently discovered these properties in the tart cherry.

Melatonin was discovered in 1958 by a dermatologist named Aaron Lerner at Yale University.

Melatonin is a natural hormone that is produced in the pineal gland located at the base of the brain. It triggers sleepiness during night hours. Melatonin production can be disrupted because of staying up at night utilizing artificial light. Melatonin has been found to decrease with age. This is why elderly people often have trouble sleeping or staying asleep at night. Stress can also cause melatonin levels to drop thus causing poor sleep and insomnia.

What Foods Contain Melatonin?

Melatonin is most plentiful in tart cherries, especially the Montmorency variety.

http://www.naturalnews.com/025210.html

I recently started taking Melatonin as well but it is contraindicated for PD?