Parallel brainstem circuit discovery suggests new path in Parkinson's research
 

After 50 or so years of dopamine theory, PD proves more illusive.
Imad

Parallel brainstem circuit discovery suggests new path in Parkinson's research
Chicago and Montreal researchers studying the lowly lamprey eel have identified an overlooked nervous system pathway running parallel to known brainstem locomotor command circuitry in vertebrates such as birds, fishes and mammals.

The finding is reported in Nature Neuroscience, online May 16, and highlighted in the magazine's "news and views" section.

Simon Alford, University of Illinois at Chicago professor of biological sciences and the article's corresponding author, said the role of a neurotransmitter associated with this parallel pathway may also suggest new research directions for treating Parkinson's disease.

Alford, along with his former graduate student and lead author Roy Smetana, now a University of Pittsburgh resident in psychiatry, worked with Université de Montréal and Université de Québec à Montréal neurobiologist Réjean Dubuc and his post-doctoral researcher Laurent Juvin in trying to sort out how the neurotransmitter analog muscarine modifies sensory information going to the brain.

Their work determined that muscarine stimulated neural activity, leading to locomotion in the laboratory lampreys.

The group focused its attention on a collection of brainstem neurons that tell the spinal cord to generate motor output that enables walking and other locomotion.

"We started looking at this group of neurons, which in the lamprey are conveniently very large, so they're easy to plant electrodes and record from," said Alford. "We discovered the muscarinic excitation was not working on these cells, but on a previously unknown group of cells within the brainstem."

Thanks for being on it, Imad, as always!

Hello, hello, from White Rats to White Coats - I've been saying, it's not just about the dopamine...

Thanks for this post......
 

The role of the neurotransmitter acetylcholine may ultimately suggest new Parkinson's disease treatments. While a key Parkinson's symptom is tremor, an advanced stage symptom is the inability to start a movement, such as walking. Symptoms associated with Parkinson's can be helped by reducing acetylcholine-mediated neurotransmission in the brain, but little work has focused on brainstem muscarine receptors in this disease.

I tried to talk about exactly this at my last appointment and was flatly told that anticholinergic medication is 'very old fashioned and out of date' . I have read that such medications were a mainstay of PD treatment prior to l-dopa, and there must have been good reasons for that. I took such three drugs for different reason than PD, over nearly 4 years, they are regularly prescribed for other conditions, and discontinued them due to side effects, and my query was because I had lost fluidity of movement since stopping them.

The consultant who prescribed them was aware that they enhanced mobility in PD.

And then this crops up!

Paula, I know you have been looking at this for ages.....

Thank you so much for this post, Imad.

Lindy

gestalt
 

here's the public press release all put together:
Public release date: 19-May-2010

Contact: Paul Francuch
francuch@uic.edu
312-996-3457
University of Illinois at Chicago

Parallel brainstem circuit discovery suggests new path in Parkinson's research


Chicago and Montreal researchers studying the lowly lamprey eel have identified an overlooked nervous system pathway running parallel to known brainstem locomotor command circuitry in vertebrates such as birds, fishes and mammals.
The finding is reported in Nature Neuroscience, online May 16, and highlighted in the magazine's "news and views" section.
Simon Alford, University of Illinois at Chicago professor of biological sciences and the article's corresponding author, said the role of a neurotransmitter associated with this parallel pathway may also suggest new research directions for treating Parkinson's disease.
Alford, along with his former graduate student and lead author Roy Smetana, now a University of Pittsburgh resident in psychiatry, worked with Université de Montréal and Université de Québec à Montréal neurobiologist Réjean Dubuc and his post-doctoral researcher Laurent Juvin in trying to sort out how the neurotransmitter analog muscarine modifies sensory information going to the brain.
Their work determined that muscarine stimulated neural activity, leading to locomotion in the laboratory lampreys.
The group focused its attention on a collection of brainstem neurons that tell the spinal cord to generate motor output that enables walking and other locomotion.
"We started looking at this group of neurons, which in the lamprey are conveniently very large, so they're easy to plant electrodes and record from," said Alford. "We discovered the muscarinic excitation was not working on these cells, but on a previously unknown group of cells within the brainstem."
What's more, these newly discovered brainstem neurons showed what Alford called a "very odd response" to the muscarine.
"Instead of just turning on -- like a synapse turns on a neuron and makes it fire -- when you put muscarine on these cells, they turn on and stay on" for a minute or longer which he said for a neurological reaction can be a very long time.
The researchers discovered the actual brain neurotransmitter that activates muscarine receptors -- another chemical, acetylcholine -- sends a signal to these newly discovered brainstem neurons, switching them on for the lengthy minute or so durations.
Alford said the finding opens up new insights into animal locomotion.
"It's a system for turning on your locomotor system and making you walk or run in a very coordinated, straight-line fashion sustaining locomotion for a considerable time," he said. "This simply was not known to exist before we discovered it."
The role of the neurotransmitter acetylcholine may ultimately suggest new Parkinson's disease treatments. While a key Parkinson's symptom is tremor, an advanced stage symptom is the inability to start a movement, such as walking. Symptoms associated with Parkinson's can be helped by reducing acetylcholine-mediated neurotransmission in the brain, but little work has focused on brainstem muscarine receptors in this disease.
"This may be a backdoor finding into a secondary effect of Parkinson's disease that's not well studied because most research emphasis has been on dopamine and the basal ganglia, a different neurotransmitter and region of the brain," Alford said.


Major funding for the research came from the National Institute of Neurological Disorders and Stroke, and the Canadian Institutes of Health Research.

http://www.eurekalert.org/pub_releas...-pbc051910.php#

Even more to try and figure out...
 

Hi all,

I am pretty sure this is where the idea that coffee may be neuroprotective comes from this largely underexplored side of PD. I have read anecdotal evidence that caffeine alleviates symptoms in some- not happening for me, but there are studies going on now. Same with targeting nicotinic receptors and whole idea behind smoking... -Laura

This excerpt is from a new find The IUPHAR Database http://www.iuphar-db.org/DATABASE/Fa...ard?familyId=2 (International Union of Pharmacology) of an association that really seems to be providing good information on receptors, disease, and emerging drug treatments:


Muscarinic receptors as drug targets

In line with a greater understanding of the neuromodulatory role of muscarinic receptors has come a greater focus on the possibility that this receptor family may be effective therapeutic targets in a number of neurological and psychiatric diseases [231]. Historically this focus has centred on Alzheimer's disease, which is associated with a loss of cholinergic innervation in the cerebral cortex and hippocampus, and is currently treated by enhancing cholinergic transmission via pharmacological inhibition of cholinesterase activity[234]. Whereas for many years this treatment was thought to have its beneficial affects by stimulation of the M1-muscarinic receptor subtype [235], work on the M1-receptor knockout mice has suggested that this receptor subtype may not play such an important role in cognition as previously thought [231]. Thus, novel anti-Alzheimer drugs that target other muscarinic receptor subtypes, such as the M2-, M4- and M5-muscarinic receptors, are now under more intense consideration. Interestingly, muscarinic receptor modulation of dopaminergic transmission has provided the impetus for the development of muscarinic receptor ligands in the treatment of schizophrenia and Parkinson's disease [231]. In both cases the focus has been on the M1 and M4-muscarinic receptors, where it has been indicated that agonists to these receptors might be beneficial in schizophrenia and antagonists are likely to be of benefit in Parkinson's disease.

I've been experimenting with coffee baths - your skin absorbs stuff apparently even more effectively in some cases, right? I think they do help.