KIbsen,

Your post keeps the percentage of people we have all talked to who say stress is a factor and affects symptoms at 100%.

paula

Aside from theories about its role in causing PD, the hormones associated with stress (cortisol, epinephrine, and norepinephrine) are themselves neurotransmitters and so are their breakdown products. Neurologists dismiss the importance of stress because that is the province of endocrinologists. Furthermore, stress can trigger inflammation which involves chemicals called cytokines and they, too, are neuroactive. But they are the territory of the immunologists. We are stuck in the crack between these three disciplines.

And, lest anyone think this is off topic, both conditions open the BBB.

Ron,
I so don’t have the background for your question so this may be way off base. I wonder if any of your BBB permeability questions have been answered in investigations of the Dopamine theories of Schizophrenia:

Neuroleptic drugs and the Blood Brain Barrier

http://www.metacrawler.com/info.meta...17/top/-/-/1/1

is a search that yields similar info on antipsychotic meds.

On the stress factor, I tremor to beat the band everytime I have to do any public speaking and my Grandfather, a brittle diabetic, ran the risk of insulin shock whenever he had to address an audience.

I’d like to learn more about BBB theories. The appeal for me is they could address PD through the ages. I downloaded an e-text of the King James version of the Bible and found dozens of references to palsy which I accept as references to PD or similar diseases. I don’t think folks during the time of Christ had worries over pesticides or pollution, however the same virus that could invade the lining of the heart muscle may permeate and cause a bruising of the brain.

Bible, King James Version
14 matches.
________________________________________
1Mac.9
1. [55] And as he began to pull down, even at that time was Alcimus plagued, and his enterprizes hindered: for his mouth was stopped, and he was taken with a palsy, so that he could no more speak any thing, nor give order concerning his house.
Matt.4
1. [24] And his fame went throughout all Syria: and they brought unto him all sick people that were taken with divers diseases and torments, and those which were possessed with devils, and those which were lunatick, and those that had the palsy; and he healed them.
Matt.8
1. [6] And saying, Lord, my servant lieth at home sick of the palsy, grievously tormented.
Matt.9
1. [2] And, behold, they brought to him a man sick of the palsy, lying on a bed: and Jesus seeing their faith said unto the sick of the palsy; Son, be of good cheer; thy sins be forgiven thee.
2. [6] But that ye may know that the Son of man hath power on earth to forgive sins, (then saith he to the sick of the palsy,) Arise, take up thy bed, and go unto thine house.
Mark.2
1. [3] And they come unto him, bringing one sick of the palsy, which was borne of four.
2. [4] And when they could not come nigh unto him for the press, they uncovered the roof where he was: and when they had broken it up, they let down the bed wherein the sick of the palsy lay.
3. [5] When Jesus saw their faith, he said unto the sick of the palsy, Son, thy sins be forgiven thee.
4. [9] Whether is it easier to say to the sick of the palsy, Thy sins be forgiven thee; or to say, Arise, and take up thy bed, and walk?
5. [10] But that ye may know that the Son of man hath power on earth to forgive sins, (he saith to the sick of the palsy,)
Luke.5
1. [18] And, behold, men brought in a bed a man which was taken with a palsy: and they sought means to bring him in, and to lay him before him.
2. [24] But that ye may know that the Son of man hath power upon earth to forgive sins, (he said unto the sick of the palsy,) I say unto thee, Arise, and take up thy couch, and go into thine house.
Acts.9
1. [33] And there he found a certain man named Aeneas, which had kept his bed eight years, and was sick of the palsy.
________________________________________

I don't understand why doctors and scientists from the different disciplines aren't working together. It seems like they do in the study of other disorders. I'm pretty tired as I write this so it's hard to think... but this just seems so wrong.

I've learned more about how to cope with PD from this forum than from any other source. It's great that the forum is exists, but it's sad that there aren't other similarly valuable sources. Of course, I'm a newbie and haven't yet been able to go to one of the high-quality clinics.

I'd like to know if there are any people who are actively engaged in the study of PD who are lurking this forum. I understand why a professional wouldn't want to express an opinion. It sure would be valuable for them to monitor our writings. Perhaps we need to give the URL to our doctors and urge (or maybe coerce) them to browse the site.

Karl,
I am in contact with a professor in the UK who is an expert on the BBB and heads a group doing research into the BBB. She is very interested in the concept, and is starting work shortly on this topic. So the cavalry is coming in the form of professional help.
wwallyo,
I have not investigated neuroleptic drugs, not quite sure what you are suggesting. As far as I know , neuroleptic drugs can be tranquilisers, so do they fight stress by reducing permeability of the BBB. Try your search adding "permeability" to your search words.
Ron

An interesting article on Epstein Barr Virus being the cause of MS and how the virus crosses the BBB.
Ashley

In the case of MS, EBV is carried across the blood-brain barrier by lymphocytes B - the cells of the immune system that make anti-bodies, Aloisi said.
"This is an extraordinary result," said ISS President Enrico Garaci.
"For the first time, the observation of a virus in the brain of MS patients has enabled researchers to explain both the characteristics and the mechanisms of the disease".

http://www.ansa.it/site/notizie/awnp...105142211.html

Re: stress

Damage to the dorsal motor nucleus occurs in PWP. However it is not involved with heart rate and stress response, that is located in the nucleus ambiguus of the vagus.
PWP also show massive loss of hypocretin/orexin neurons in the hypothalamus (pdf). I propose this is a likely mechanism by which the stress response in PWP is amplified:

Hypocretin-1 (Orexin-A) Facilitates Inhibitory and Diminishes Excitatory Synaptic Pathways to Cardiac Vagal Neurons in the Nucleus Ambiguus

Hypocretin-1 is a neuropeptide recently shown to be involved in autonomic regulation. Hypocretin-1 is expressed by hypothalamic neurons, which project to many regions of the central nervous system, including the nucleus ambiguus. One possible site of action of hypocretin-1 could be cardioinhibitory parasympathetic vagal neurons within the nucleus ambiguus. This study examines whether hypocretin-1 modulates inhibitory and excitatory postsynaptic currents in cardiac vagal neurons in the rat nucleus ambiguus. GABAergic, glycinergic, and glutamatergic activity to cardiac vagal neurons was examined using whole-cell patch-clamp recordings in an in vitro brain slice preparation. Hypocretin-1 (1 µM) produced a significant increase in the frequency and amplitude of both GABAergic and glycinergic inhibitory postsynaptic currents and a significant decrease in the frequency of glutamatergic excitatory postsynaptic currents. Application of tetrodotoxin (0.5 µM) blocked all of the responses to hypocretin-1, indicating the changes in neurotransmission with hypocretin-1 do not occur at presynaptic terminals but rather occur at the preceding GABAergic, glycinergic, and glutamatergic neurons that project to cardiac vagal neurons. The increase in GABAergic and glycinergic inhibitory postsynaptic currents, and the decrease in glutamatergic excitatory postsynaptic currents, could be mechanisms by which hypocretin-1 affects heart rate and cardiac function.

(I have never been able to speak in public. My heart would race and my vision would constrict and I was unable to see my notes. Until recently I couldn't even post on online forums, the stress would give me tics for days.)

Ron;
15 years ago, I did a lot of reading on theories of the causes of Schizophrenia and why standard antipsychotic medications are suspected to work. Crudely put, the broad thought was that too much dopamine leads to auditory and visual hallucinations and psychosis. These major antipsychotic medications inhibit or slow down the processing of dopamine. The drugs used to control schizophrenia may share similar problems with Parkinson’s Disease treatment i.e. trying to regulate dopamine and ending up with too much dopamine or not enough. Look at, for example how many PD meds cause symptoms related to psychosis/ depression or how many things go wrong when we get too much dopamine. Chlorpromazine came out in the 50’s so surely the BBB must have been examined in Chlorpromazine’s development and subsequent decades of use. The discussion below ties Schizophrenia and Parkinson’s Disease on a few points. It is also interesting to note that prolonged use of anti-psychotic medications causes tardive dyskenesia and other parkinsonian features. These medications inhibit dopamine. Your discussion on BBB and permeability may be enlightened by examining Schizophrenia and the ways antipsychotic drugs work.

I pulled the following from:
http://www.benbest.com/science/anatmind/anatmd10.html

Phenothiazine derivatives
Phenothiazine: One of a group of tranquilizing drugs with antipsychotic actions thought to act by blocking dopaminergic transmission (messages sent using the substance dopamine) within the brain.
Schizophrenia is thought to be due to an overstimulation of D2 receptors in the mesolimbic and mesocortical systems. Evidence for the "excess dopamine" theory of schizophrenia comes largely from the fact that D2 antagonist drugs alleviate the symptoms, whereas substances which increase D2 stimulation, such as amphetamines, can induce psychotic symptoms (which are reversible with D2 antagonists). About 10% of Parkinsonian patients given DOPA treatment will develop psychotic symptoms resembling schizophrenia.
The major classes of antipsychotic drugs are the phenothiazines (e.g., chlorpromazine), the butyrophenones (e.g., haloperidol) and the thioxanthenes (e.g., chlorprothixene). Butyrophenones are 100 times more potent against D2 receptors than against D1 receptors. The similarity in shape between a portion of the chlorpromazine molecule and dopamine indicates how chlorpromazine could bind to a dopamine receptor without triggering a response.
The mesolimbic & mesocortical dopaminergic systems are thought to play an important role in motivation, by attaching cognition of incentive significance to stimuli. In experiments on animals that are motivated to electrically self-stimulate themselves with electrodes implanted in their brains, dopamine is the mediating neurotransmitter for the locus ceruleus, lateral hypothalamus, ventral tegmental area and sulcal prefrontal cortex (but not the nucleus accumbens or substantia nigra).
Cocaine particularly increases dopaminergic activity in the mesolimbic areas of the brain by inhibiting dopamine re-uptake in the ventral tegmental area and the nucleus accumbens. Amphetamine seems more generalized in its action, not only by inhibiting re-uptake, but by releasing dopamine from most brain regions. Both cocaine & amphetamine produce feelings of psychological energy & arousal, associated with diminished appetite & need for sleep. Both cocaine & amphetamine can lead to visual & tactile hallucinations as well as paranoid thinking, although the psychotic effects of amphetamine may also be mediated by increased serotonin release. Chronic amphetamine users seem to lose a capacity for normal pleasure -- which has been correlated with neuron degeneration in the mesolimbic area.
Perception of time-intervals is believed to be mediated by spiny neurons located in the striatum of the basal ganglia. Timing begins with a burst of dopamine and ends with a recognized signal. Marijuana slows subjective time by lowering dopamine available, whereas cocaine and methamphetamine accelerates the sense of time by increasing dopamine availability. (Adrenaline and stress hormones can also "make seconds feel like hours".)
There is no answer required to what I’ve written here, but I believe it would be a service to your UK professor to consider Manic Depression, Schizophrenia, theories re: Dopamine, theories of the disease and tardive dyskenesia and parkinsonian damage from long term use of phenothiazines. She may find some of the leg work already done. Wish I knew more. When God creates a 48 hour day . ... Guy

wwallyo,
Thanks, I will pass your information to the Prof. I am excited to get professional help on the BBB concept at last.
Ron

1: Neurobiol Dis. 2000 Aug;7(4):429-47.

The single intranigral injection of LPS as a new model for studying the
selective effects of inflammatory reactions on dopaminergic system.

Herrera AJ, Castano A, Venero JL, Cano J, Machado A.

Departamento de Bioquimica, Bromatologia, Toxicologia, y Medicina Legal,
Universidad de Sevilla, Calle Prof., Garcia Gonzalez s/n, Sevilla, 41012, Spain.

We have injected lipopolysaccharide (LPS) into the nigrostriatal pathway of rats
in order to address the role of inflammation in Parkinson's disease (PD). LPS
induced a strong macrophage/microglial reaction in Substantia nigra (SN), with a
characteristic clustering of macrophage cells around blood-vessels. The SN was
far more sensitive than the striatum to the inflammatory stimulus. Moreover,
only the dopaminergic neurons of the SN were affected, with no detectable damage
to either the GABAergic or the serotoninergic neurons. The damage to the DA
neurons in the SN was permanent, as observed 1 year postinjection. Unlike the
direct death of dopaminergic neurons caused by agents as MPP(+) or 6-OHDA, LPS
seems to cause indirect death due to inflammatory reaction. Therefore, we
suggest that the injection of a single dose of LPS within the SN is an
interesting model for studying the selective effects of inflammatory reaction on
dopaminergic system and also potentially useful for studying PD. Copyright 2000
Academic Press.

PMID: 10964613 [PubMed - indexed for MEDLINE]


So the immune response to the presence of the bacterial toxin is to surround the blood vessels (i.e. the BBB) ? Interesting, no?