[reverett123]

As most of you know ad nauseum I have been beating the drum for a combined attack by the immune system causing neuroinflammation further aggravated by stress as the central driver for PD. This short piece in today's Science Daily not only makes the last pieces fit, it offers a promising treatment with a very old, cheap, and (safe) time=tested drug.

"Researchers See a 'Picture' of Threat in the Brain: Work May Lead to New Model of Neuroinflammation

ScienceDaily (May 3, 2011) — A team of researchers is beginning to see exactly what the response to threats looks like in the brain at the cellular and molecular levels.

This new information, including the discovery that a model of social stress can increase inflammation among brain cells, should provide new insight into how the stress response affects inflammatory and behavioral responses.

It may also provide new targets for drugs treatments in the continuing struggle to curtail depression and anxiety.

Scientists from Ohio State University's Institute of Behavioral Medicine Research reported their results in the latest issue of the Journal of Neuroscience....

"These animals can't flee, so they have to stand and fight," Sheridan explained. "In doing so, they're repeatedly defeated, creating a condition called "learned helplessness," a condition closely linked to depression.

What Sheridan and Godbout saw was that the animals' anxiety continued for a long time after the termination of the stressful episodes of defeat. "For two weeks or more after we stopped the stressor, we could still see this anxiety-like behavior," Sheridan said.

The real discoveries came when the researchers analyzed what was happening in the animals' brains and in their immune response.

"We found that in the stressed animals, a certain type of immune cell (myeloid progenitor cell, or MPC), produced in the bone marrow, entered the circulatory system and migrated to the brain," explained Godbout.

These MPCs might normally relocate in this way to deal with an infection or an injury in the brain, but in this case, they moved solely because of the response to a social stressor, he said. The experiments showed that the number of these cells more than tripled in the brain following the stress.

Other immune cells called microglia, normally residing in the brain, also triggered an inflammatory response because of the stress. The researchers also noted that the stressor caused a particular activation pattern of neurons, or nerve cells, within the brain.

The response to social stress also caused an increase in the amounts of some inflammatory cytokines in the brain, including interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-a) which are linked to inflammation. These cytokine responses correlated with an insensitivity of MPCs to glucocorticoids, hormones that normally inhibit inflammation in the body....

So the research team saw these and other cellular changes occurring in the brain following the stress, at the same time they were seeing the behavioral changes -- the anxiety-like behavior.

The findings are evidence of a two-way communication that's existing between the body and the brain in times of stress, Sheridan said.

To test that apparent connection, they gave the mice injections of propranolol -- a so-called "beta-blocker" drug often used for cardiac conditions -- before they encountered the more aggressive mouse. In this case, the researchers saw no increase in IL-1 or TNF-a, no glucocorticoid insensitivity, and no long-lasting anxiety-like behavior in the test animals.

"If we treated the animal with a beta-blocker each night before we put the intruder in, it completely blocked the signal. The anxiety-like behavior never developed," Godbout said.

"What this basically argues is that we may now have a new target for individuals who have extended anxiety-like behavior," Sheridan said. "We may have a new target cell to think about in terms of new therapies...."

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Propranolol is an interesting drug. By coincidence I began taking it about three months ago as part of dealing with the problems that I was having with potassium shifts.
From Wikipedia-
"Propranolol is one of the banned substances in the Olympics, presumably for its use in controlling stage fright and tremors. It was taken by Kim Jong Su, a North Korean pistol shooter who won two medals at the 2008 Olympic Games. He was the first Olympic shooter to be disqualified for drug use.[1]....
"Propranolol is often used by musicians and other performers to prevent stage fright. It has been taken by surgeons to reduce their own innate hand tremors during surgery.[9]

Propranolol 80mg daily should be used post discharge in STEMI patients.

Propranolol is currently being investigated as a potential treatment for post-traumatic stress disorder.[10][11][12] Propranolol works to inhibit the actions of norepinephrine, a neurotransmitter that enhances memory consolidation. Studies have shown that individuals given propranolol immediately after a traumatic experience show less severe symptoms of PTSD compared to their respective control groups that did not receive the drug (Vaiva et al., 2003)....

[imark3000]

Thank you Rick for the very interesting post.
I will digress a little and deal with the subject in a more general way.

In most cases, anxiety, which is really a disguised or undisguised fear, starts in very early childhood (in some cases even before birth) and often the problem runs in families.
Children will develop this malady as a result of one or more traumatic experiences but more often it happens in “ideal” families over many years. The core of the problem is not so much due to the severity of the physical or psychological hurt that is inflicted on the child BUT rather on weather the family environment allowed the child to cry out the pain or suppress it.
Suppressed pain changes the brain circuitry and haunts the person all his life.
Often the person with neurotic anxiety may appear quite calm and pleasant but that is only achieved by always overworking the brain to suppress the painful memories deeply imbedded. The normal stresses of life are exaggerated by the anxious person because, subconsciously, it threatens to bring to the surface tightly imprisoned and guarded pains which were conceived in childhood to be life threatening.

I am afraid that it is a lost battle with anxiety. Because even when adopting the least stressful life style, the person will invent stress from normal or trivial incidents.

I have suffered myself from this problem and became aware of it since my teens. I have read many books about it. But I am afraid that understanding this problem does not help a bit in resolving it!!

In a superficial way, it may appear that I have conquered anxiety as I have managed to lead what appears to be a normal life ..2 university degrees ..happy family .. children and grand children, etc. but I guess that my brain had to fight an internal battle all along. Parkinson’s disease, I knew, was a cry of an overworked brain demanding a holiday or even retirement!

By the way, I took Beta blocker (Inderal) for 5 years, 1990-1995, as treatment for hypertension and high BP with no side effects. It is also used as treatment for tremor, and I am going to ask my neuro to prescribe it for me.

cheers
Imad

[reverett123]

Imad-

I couldn't agree with you more. Childhood trauma and pain is only now being recognized for the killer it actually is. I find it interesting that the beta-blockers are being used with PTSD as well.

[aquario]

When I was diagnosed 5 years ago, my family practitioner said I might want to try Inderal/propanolol as it's often used for essential tremor, and might help with pd. I teach at a university and take one 20 mg pill before going into classes, and it has been very beneficial in masking my most visible symptom. No side effects, cheap, been around for ages, and I have classical musician friends who swear by it for stage nerves. It's definitely been an ally.