[reverett123]

You may not have noticed, but I have a thing about stress and PD. Both cause and complication, Anne Frobert and I concluded that it was the elephant in the room with little research being done. I went so far as to claim a link to the fetal environment. I have found a "real" scientist, MJ Zigmond, who has been on the same trail since 1981 with two dozen papers on it.


1: Stress. 2008;11(6):448-56.

Maternal separation exaggerates the toxic effects of 6-hydroxydopamine in rats:
implications for neurodegenerative disorders.

Pienaar IS, Kellaway LA, Russell VA, Smith AD, Stein DJ, Zigmond MJ, Daniels WM.

Division of Medical Physiology, Department of Biomedical Sciences, University of
Stellenbosch, Tygerberg, South Africa.

Many studies have shown that early life stress may lead to impaired brain
development, and may be a risk factor for developing psychiatric pathologies such
as depression. However, few studies have investigated the impact that early life
stress might have on the onset and development of neurodegenerative disorders,
such as Parkinson's disease, which is characterized in part by the degeneration
of dopaminergic neurons in the nigrostriatal pathway. The present study subjected
rat pups to a maternal separation paradigm that has been shown to model adverse
early life events, and investigated the effects that it has on motor deficits
induced by a unilateral, intrastriatal injection of 6-hydroxydopamine (12
microg/4 microl). The female rats were assessed for behavioral changes at 28 days
post-lesion with a battery of tests that are sensitive to the degree of dopamine
loss. The results showed that rats that had been subjected to maternal separation
display significantly impaired performance in the vibrissae and single-limb
akinesia test when compared to normally reared animals. In addition, there was a
significant increase in the loss of tyrosine hydroxylase staining in maternally
separated rats. Our results therefore suggest that adverse experiences sustained
during early life contribute to making dopamine neurons more susceptible to
subsequent insults occurring during more mature stages of life and may therefore
play a role in the etiopathogenesis of Parkinson's disease.


PMID: 18609296 [PubMed - indexed for MEDLINE]

[lurkingforacure]

Some years back my neighbors shared a book with me about this, but it was focused on the development of something called the limbic system. If I remember correctly, the gist was that if the infant is not allowed to be with its mother, the limbic system does not develop properly and the individual has problems later on. Mainly the problems were emotional and social, but clearly our intellectual development depends upon how happy we are, at least IMHO. It was fascinating. I wish I could remember the name of the book, or the authors, sorry.

[girija]

Rick,
I do agree with you that stress has a lot of effect on how PD progresses and have personal experiences to believe in it. Friday I was doing great, all set to conquer the world! Saturday morning I find out that my new health insurance policy has a huge deductible for name brand meds. I was shocked when the pharmacy said I had to pay 230$$ for Azilect. That was the trigger, within a couple of hours, my symptoms got so bad, whole body was stiff, I couldnt move, missed fireworks too. Such rapid changes, I could not believe it myself.

Now, just a word of caution about Pubmed papers/ If there are papers on a subject from 1981 and still there are only a handful of them in 2009 , it tells you something. Either the observations are nothing unique to PD, or the science behind the phenomenon is not understood well and is still too complicated to explain. If everything alright, you would find many more papers. DO you know if people with other neurological or neuromuscular disorders respond to stress the same way we do??

Oh, before I forget, regarding the Himalayan product, I will go thru the abstracts and let you know in a couple of days.

thanks
girija






QUOTE=reverett123;533105]You may not have noticed, but I have a thing about stress and PD. Both cause and complication, Anne Frobert and I concluded that it was the elephant in the room with little research being done. I went so far as to claim a link to the fetal environment. I have found a "real" scientist, MJ Zigmond, who has been on the same trail since 1981 with two dozen papers on it.


1: Stress. 2008;11(6):448-56.

Maternal separation exaggerates the toxic effects of 6-hydroxydopamine in rats:
implications for neurodegenerative disorders.

Pienaar IS, Kellaway LA, Russell VA, Smith AD, Stein DJ, Zigmond MJ, Daniels WM.

Division of Medical Physiology, Department of Biomedical Sciences, University of
Stellenbosch, Tygerberg, South Africa.

Many studies have shown that early life stress may lead to impaired brain
development, and may be a risk factor for developing psychiatric pathologies such
as depression. However, few studies have investigated the impact that early life
stress might have on the onset and development of neurodegenerative disorders,
such as Parkinson's disease, which is characterized in part by the degeneration
of dopaminergic neurons in the nigrostriatal pathway. The present study subjected
rat pups to a maternal separation paradigm that has been shown to model adverse
early life events, and investigated the effects that it has on motor deficits
induced by a unilateral, intrastriatal injection of 6-hydroxydopamine (12
microg/4 microl). The female rats were assessed for behavioral changes at 28 days
post-lesion with a battery of tests that are sensitive to the degree of dopamine
loss. The results showed that rats that had been subjected to maternal separation
display significantly impaired performance in the vibrissae and single-limb
akinesia test when compared to normally reared animals. In addition, there was a
significant increase in the loss of tyrosine hydroxylase staining in maternally
separated rats. Our results therefore suggest that adverse experiences sustained
during early life contribute to making dopamine neurons more susceptible to
subsequent insults occurring during more mature stages of life and may therefore
play a role in the etiopathogenesis of Parkinson's disease.


PMID: 18609296 [PubMed - indexed for MEDLINE][/QUOTE]

[indigogo]

Michael Zigmond is a familiar research face; he is currently at University of Pittburgh. He has recently been engaged in excercise and neuroprotection research in PD; works frequently with all of the orgs.

http://www.neurology.upmc.edu/faculty/zigmond.html

Personally, stress management is my key to symptom control.

[reverett123]

Girija, like you, I began my little quest with the assumption that if the stress/PD link was real and important that it would be reflected in the literature. Finding that it was not made me sit up and realize that if something that pervasive was not integrated into the field that there might be some pretty powerful things to be gained once it was done so.

You experienced one aspect of the link, the exacerbation of symptoms by acute stress. If you look at the literature you will find very little on the subject, despite the fact that it is near universal. How can this be? My own theory is that PD is considered a neurological disorder and the stress system is considered to be the realm of endocrinology. There is little communication across the boundaries of the disciplines, not due to lack of interest but due to the sheer volume of data to be kept up with in either field. No one has had time to follow up on anecdotal reports from patients. And, as has been noted, researchers don't interact with patients anyway.

Now, that may or may not be true. But you experienced it. It exists and isn't well accounted for and may be terribly important. For example, the question of whether to retire early or not could be answered here.

And that is just one area. Others include acute stress as a trigger for worsening symptoms, chronic stress as causal, life-trauma effects at various ages, fetal exposure to maternal stress hormones, and, even, maternal stress pre-conception! There is a strong case to be made for each as a factor in PD. But the research has not been done! And, if that be true, there is a potential wealth of data to be gathered.


1: Physiol Behav. 2002 Dec;77(4-5):527-31.

Stress-induced Parkinson's disease: a working hypothesis.

Smith AD, Castro SL, Zigmond MJ.

Department of Neurology, University of Pittsburgh, S-526 Biomedical Science
Tower, 15212, Pittsburgh, PA, USA.

Some cases of Parkinson's disease (PD) can be attributed to genetic mutations,
others to specific environmental factors; yet the cause of a great majority of
cases is unknown. Physical and emotional traumas were once briefly considered as
factors in the pathophysiology of this disorder. With increasing evidence that
stress can indeed increase neuronal loss in some brain regions, this hypothesis
deserves to be reexamined. Stress increases the extracellular availability of
glucocorticoids (GCs), dopamine (DA), and glutamate in the striatum as well as
other brain regions. These factors undoubtedly can serve to enhance the functions
of the striatum. However, each also has the capacity to be neurotoxic. Moreover,
they can act synergistically to promote neuronal loss. Thus, we propose that
stress might, indeed, be a key factor in the loss of DA neurons that underlies
PD.


PMID: 12526994 [PubMed - indexed for MEDLINE]

[Ronhutton]

Hi Rick,
Don't forget stress increases considerably the permeability of the blood-brain barrier. That is why it exacerbates the symptoms of not only PD but other neuro illnesses as well.
Ron

[Heidi L]

Stress has been shown to increase permeability of the blood-brain-barrier.
Reactivation of Herpesvirus1 in rabbit brains resulted in a breakdown of the blood-brain barrier.
HSV-1 is shown to reactivate in rats subjected to stress.
Neuronal excitation status may dictate the efficiency of HSV-1 viral replication.
Findings strongly support the concept that stress induces HSV-1 reactivation from latency at least in part by compromising CD8+ T cell surveillance of latently infected neurons.

______________________________________

References:
Stress-induced increase in blood-brain barrier permeability in control and monosodium glutamate-treated rats.
Skultétyová I, Tokarev D, Jezová D.
Brain Res Bull. 1998;45(2):175-8.

Spread of herpes simplex virus type 1 in the central nervous system during experimentally reactivated encephalitis.
Stroop WG, McKendall RR, Battles EJ, Schaefer DC, Jones B.
Microb Pathog. 1990 Feb;8(2):119-34.

Role of the hypothalamic pituitary adrenal axis and IL-6 in stress-induced reactivation of latent herpes simplex virus type 1.
Noisakran S, Halford WP, Veress L, Carr DJ.
J Immunol. 1998 Jun 1;160(11):5441-7.

Neuronal activity regulates viral replication of herpes simplex virus type 1 in the nervous system.
Zhang CX, Ofiyai H, He M, Bu X, Wen Y, Jia W.
J Neurovirol. 2005 Jul;11(3):256-64.

Psychological stress compromises CD8+ T cell control of latent herpes simplex virus type 1 infections.
Freeman ML, Sheridan BS, Bonneau RH, Hendricks RL.
J Immunol. 2007 Jul 1;179(1):322-8.


Please read my paper.