PD as a broadband problem
 

We have talked about problems with multitasking, sensory overload, etc. And while we have been taught to think in terms of a chemical shortage, a lot of us have vague suspicions.

If we think for a minute of dopamine as the shuttle bus carrying information from one cell to the next, then we are envisioning a shortage of shuttle buses and we try to increase their number. But, what if we think in terms of the problem being a lack of enough good roads for the buses instead? After all, a hundred buses will do you little good if your system saturates at ten.

This was triggered by a report this morning in Science Daily -
"In human and mouse brains, kalirin is the brain protein needed to build the dense network of highways, called dendritic spines, which allow information to flow from one neuron to another. Northwestern scientists have found that without adequate kalirin, the frontal cortex of the brain of a person with schizophrenia only has a few narrow roads. The information from neurons gets jammed up like rush hour traffic on an interstate highway squeezed to a single lane.

"Without enough pathways, the information takes much longer to travel between neurons and much of it will never arrive," said Peter Penzes, assistant professor of physiology at the Feinberg School. He is senior author of a paper reporting the findings published in a recent issue of the Proceedings of the National Academy of Science. Michael Cahill, a Feinberg doctoral student in neuroscience, is the lead author."

Finally, what makes this doubly interesting to me are reports like this one:

1: Jpn J Pharmacol. 2002 Nov;90(3):254-62.

Axonal and dendritic extension by protopanaxadiol-type saponins from ginseng
drugs in SK-N-SH cells.

Tohda C, Matsumoto N, Zou K, Meselhy MR, Komatsu K.

Research Center for Ethnomedicines, Institute of Natural Medicine, Toyama
Medical and Pharmaceutical University, Toyama, Japan.

Extension of axons and dendrites in neurons may compensate for and repair
damaged neuronal networks in the dementia brain. To find out drugs capable of
regenerating the neuronal network, we focused on several herbal drugs belonging
to the genus Panax, kinds of Ginseng, and investigated neurite outgrowth
activity of their extracts and compounds. We found that the methanol extracts of
Ginseng (root of P. ginseng), Notoginseng (root of P. notoginseng) and Ye-Sanchi
in Chinese (rhizome of a relative to P. vietnamensis) increased neurite
outgrowth in SK-N-SH cells. The protopanaxadiol-type saponins, ginsenosides
Rb(1) and Rb(3), and notoginsenosides R(4) and Fa isolated from Ye-Sanchi
extract extended neurites, while protopanaxatriol-, ocotillol- and oleanane-type
saponins had no effect on the neurite outgrowth. The percentage of cells with
multipolar neurites and number of varicosities were intensely high in cells
treated with the methanol extract of Ye-Sanchi as well as ginsenosides Rb(1) and
Rb(3), and notoginsenosides R(4) and Fa. Both phosphorylated NF-H-expressing
neurites and MAP2-expressing ones were extended by treatment with those saponins
and the extract. Especially, longer neurites were mainly positive for
phosphorylated NF-H. These results suggest that protopanaxadiol-type saponins
enhance axonal and dendritic formation activity.

PMID: 12499580 [PubMed - indexed for MEDLINE]

getting closer
 

YES, I have in image of all the research scientists walking in circles around the solution to a cure for PD, each scientist with a correct piece of the puzzle - all they need worldwide is to put the whole puzzle together, and they will all be amazed at the simplicity of the solution.
Wishful thinking - I have always thought that a pill will be found to fix our circuits and connections, a pill that cures us and restores what many think has died, but what I think is just dormant for lack of that one pill that will be found.
I hope to say I told you so!!!!!!!

This is really fascinating. The traffic jam model resonates.

You should be a teacher!
 

I think you may be on to something. By the way, I love your metaphor, but why then would putting extra cars (dopamine) help the situation even fleetingly (as Sinemet does)? If it is the pathways transporting the cars or dopamine that cause the problem, things would just get more jammed.

Ann

Let me think a minute...
We have multiple limiting factors-
Number of roads / dendrites
Number of shuttles / dopamine supply

There is no limit on passengers because the other bottlenecks kick in well in advance. So we want to max out the number of shuttles at any one time.

When we come in to the office in the morning, it takes a little time to get shuttles out the door and onto the roads. During this phase, extra dopamine helps becaue the roads are clear. But as the roads fill, the shuttles have to line up at the gate and watch for a chance to merge into the traffic. In this phase additional shuttles do no good. In fact, it might make it worse. But as things fluctuate the line of shuttles drops and more gaps open up. During this phase, extra dopamine can be used and more shuttles hit the road.

So long as we keep buying shuttles our benefits are limited. If we could find a way to build more roads, however....

Festination and not being able to write a whole word feel like traffic jams.

paula

Rick,
Excellent way to describe a PD brain! I am way too familiar with traffic problems (I come from India and live in Southern California:)) and makes perfect sense to me! I would add to your description one more thing. Lack or mismanagement of funds (growth factors/enzymes/mutated proteins), resulted in bumpy roads or some roads dont exist anymore......

This concept fits well with Ceregene observations that their gene therapy part worked i.e., protein is made, but something is missing in its transport.

This is a good week for PD research! This paper and the other two, one on flu virus causing PD-like symptoms and the other one Ron posted on intranasal inoculation of stem cells......well, may be the light at the end of the tunnel is real, not of a incoming train!!

girija

Excellent Analogy and imagery
 

A well thought out analogy that takes into account both the bottlenecks of "passenger load" and "bandwidth."

can we expand this?
 

I was thinking that this could be useful, for newbies in particular. If anyone has further suggestions, please post them. I will rewrite and post as a sticky.