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Specific Dopamine-producing Neurons Crucial to Adaptive Movement, Early Study Finds

motor skills and Parkinson's

Dopaminergic neurons — nerve cells gradually lost to Parkinson’s progression — that contain an enzyme called aldehyde dehydrogenase 1A1 are essential for acquiring the motor skills needed for proper movement in given situations, a mouse study reports.

The research, “Distinct connectivity and functionality of aldehyde dehydrogenase 1A1-positive nigrostriatal dopaminergic neurons in motor learning,” was published in Cell Reports. The work was developed by the Intramural Research Program of the National Institute on Aging (IRP-NIA).

Parkinson’s disease severely affects dopaminergic neurons, those that produce dopamine, a neurotransmitter (cell-signaling molecule) that relays information between nerve cells and between the brain and the rest of the body.  These neurons are found in two specific brain regions involved in motor control: the striatum and the substantia nigra.

Nerve cells may or not contain aldehyde dehydrogenase 1A1 (ALDH1A1), an enzyme that is involved in cellular detoxification. Parkinson’s seems to mostly damage ALDH1A1-positive dopaminergic neurons, suggesting the enzyme may be a key player in this neurodegenerative disorder.

Both ALDH1A1-positive and ALDH1A1-negative dopaminergic nerve cells contribute to voluntary motor behavior. But the degree to which ALDH1A1-positive neurons are crucial to acquiring motor skills remains to be understood.

Using a mouse model of Parkinson’s, scientists targeted  dopaminergic neurons positive for ALDH1A1, and produced a detailed connectivity map of these specific neuronal networks in the mouse brain.

ALDH1A1-positive neurons were found to be in constant communication with other brain structures there. Importantly, researchers found that those dopamine-producing neurons of the striatum and substantia nigra that received the greatest percentage of molecular information (input) were located in the caudate-putamen nuclei, a brain region involved in movement control.

Researchers then selectively removed ALDH1A1-positive neurons to mimic the degeneration pattern observed in late-stage Parkinson’s disease. The animals’ ability to show new motor skills — new ways of voluntary movement, like foot position for maintaining balance while walking on a moving surface — was assessed using the rotarod test. In this test, mice must learn to balance while walking on a constantly rotating rod much like a treadmill.

Mice without ALDH1A1-positive neurons displayed a distinctly poorer ability to learn new motor skills, and slower walking speeds compared to control animals.

“Compared with a modest reduction in high-speed walking, the ALDH1A1+ nDAN-ablated mice showed a more severe impairment in rotarod motor skill leaning,” the researchers wrote. “Unlike control animals … [these] mice essentially failed to improve their performance during the course of rotarod tests.” (nDANs are nigrostriatal dopaminergic neurons.)

These animals were then treated with dopamine replacement therapy, either levodopa or a dopamine receptor agonist, one hour before a new motor skills assessment. Dopamine replacement therapy is standard treatment for the motor symptoms associated with Parkinson’s.

Levodopa (L-DOPA) treatment allowed the animals without ALDH1A1-positive neurons to travel longer distances, and to walk more frequently at higher speeds during a session. But it failed to improve their ability to acquire new motor skills during repeated tests. Treatment with a dopamine receptor agonist was also ineffective.

“When the ALDH1A1+ nDANs were ablated after the mice had reached maximal performance, the ablation no longer affected the test results, supporting an essential function of ALDH1A1+ nDANs in the acquisition of skilled movements. These findings are in line with the theory that nigrostriatal dopamine serves as the key feedback cue for reinforcement learning,” the researchers wrote.

These results provide “a comprehensive whole-brain connectivity map,” they concluded, and reveal a key role of ALDH1A1-positive neurons in newly learned motor skills, suggesting that motor learning processes require these neurons to receive a multitude of information from other nerve cells and to supply dopamine with “dynamic precision.”

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My Struggles Worsen Despite Natural Treatment Experimentation

struggles

My body does not feel right. What am I going to do about it?

What has happened to me?

My quality of life was deteriorating due to my neurological issues. Along with poor fine motor skills on my left side and slowness of movement, I was constantly fatigued. This was a fatigue that no amount of quality sleep could ever satisfy. Additionally, I had internal tremors (not visible to the naked eye, but I always felt so weak and shaky). I thought for sure there must be some kind of “natural” solution to help cure what ailed me — one that did not involve prescription drugs.

My initial approach was to go to physical and occupational therapy and to continue my exercise regimen (weights, yoga, cycling, walking). This plan did not seem to slow disease progression or alleviate my symptoms. My depression and lack of motivation (other Parkinson’s disease symptoms) were also hindering me.

I can’t fight this alone, so drugs are an option

In March 2016, I finally agreed to try Azilect (rasagiline), a prescription medication. Two weeks later, my symptoms had not improved and I felt worse (dizzy and nauseous). So, off that medication and on to the next one, ropinirole. This time, it only took a few hours on the medication for me to become extremely sick with vomiting and a pounding headache. I immediately discontinued that medication.

Both my neurologist and primary care physician thought I should focus on treating my depression symptoms with a prescription medication. In August 2016, I tried Viibyrd (vilazodone HCI), an antidepressant. Within a few weeks, I was suffering from intense, gory nightmares every night with no improvement in my symptoms. At this point, I decided my PD symptoms may not be such a bad thing, and I refused to try any more medications.

I can’t fight this alone, but drugs are not an option

In October 2016, I attended a week-long workshop that focused on a plant-based diet. My diet needed a serious overhaul. The time was right to see if changing my eating habits would make a difference in the quality of my life. I was already a vegetarian, but I still loved my dairy products. I also loved sugar, pasta, and bread. These food items are known to potentially cause inflammatory responses in the body. Also, I have read that the neurodegeneration observed in PD is accompanied by inflammatory processes. If I added these two theories together, I believed a change to a gluten-free, no-sugar-added, vegan diet might help my PD symptoms.

A holistic doctor at the plant-based diet workshop I attended suggested I look into the Hinz Protocol for treating my PD. Dr. Marty Hinz developed an amino acid therapy that utilized natural dopamine powder from the Mucuna pruriens (velvet bean) plant in conjunction with other amino acids. I found a neurologist in New York City who endorsed this approach. After I returned home from the workshop, I maintained the strict diet and struggled with the Hinz Protocol. I say “struggle” because I suffered a lot of nausea. The doctor had to repeatedly adjust the dosages for the amino acid capsules and Mucuna pruriens powder to attempt to eliminate nausea and get symptom relief. Also, the cost of this protocol was hundreds of dollars per month and was not covered by insurance. I could handle the cost if my stomach had relief and my PD symptoms improved. However, that was not to be. After six months, I discontinued the Hinz Protocol.

The losses and the adjustments

I was starting to get very good at making adjustments when a PD symptom would impair me in some way. As an example, I find it difficult to put my coat on with my left sleeve first, so now I put my coat on with my right sleeve first. Or, since I can no longer feel where to put in my pierced earrings, I just make sure I have a mirror handy to see what I am doing. While waiting on a cashier’s line to check out, I make sure I have my money ready so I am not fumbling around in my purse and holding up the line. Wearing satin pajamas makes it easier to move around in bed at night. Being mindful of all my movements is critical so I do not trip, walk into things, or let things fall through my hands.

If my PD does not progress any further, I feel I can deal with the losses it has thrust upon me thus far. However, at times when I wake up in the morning, I think to myself, “What simple task will elude me today?” PD is a disease of loss, the loss of some of the most, mundane things in life many of us (including myself) take for granted. These include:

  • Holding a purse or newspaper firmly under the arm
  • Folding laundry
  • Tying shoes
  • Buttoning a shirt
  • Putting on a seat belt
  • Zipping a jacket
  • Opening a package
  • Cutting a salad

These are mindless tasks everyone does almost every day. Many of us with PD can no longer perform these daily rituals without assistance. If PD has not totally disabled us, some of us may still complete the task unassisted, but it requires intense concentration and focus on our part. It is almost as if we have reverted to being a child again.

Still struggling

It is now mid-2017. I continue to struggle with my worsening PD symptoms, and I am still not on any prescription medications.

All the “snake oil” solutions online make it even more difficult to find relief from my symptoms. On more than one of my PD-related blog posts, some unscrupulous individuals have responded with comments about the great herbal or vitamin supplement that has “cured” their PD. There are so many scammers out there, people and companies that prey on those who are so desperate for relief. I think I can speak for many of us with PD when I say we want to believe there is one thing that can help our symptoms or cure our disease, however, it is so difficult to separate what works and what doesn’t work.

Although I continue to exercise, meditate, and maintain my vegan diet, I fully realize I need more help.

Stop the roller coaster — I want to get off!

***

Note: Parkinson’s News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. The opinions expressed in this column are not those of Parkinson’s News Today or its parent company, BioNews Services, and are intended to spark discussion about issues pertaining to Parkinson’s disease.

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Source: Parkinson's News Today