Of Mice and Men

It remains to be seen if the success with mice can also be incorporated in humans. But the implications from this recent Press Release from the University of California in San Diego are incouraging.

June 24, 2020 | By Heather Buschman, PhD

One-Time Treatment Generates New Neurons, Eliminates Parkinson’s Disease in Mice

Inhibiting a single gene converts many cell types directly into dopamine-producing neurons

Left: mouse astrocytes (green) before reprogramming; Right: neurons (red) induced from mouse astrocytes after reprogramming with PTB antisense oligonucleotide treatment.

Xiang-Dong Fu, PhD, has never been more excited about something in his entire career. He has long studied the basic biology of RNA, a genetic cousin of DNA, and the proteins that bind it. But a single discovery has launched Fu into a completely new field: neuroscience. 

For decades, Fu and his team at University of California San Diego School of Medicine studied a protein called PTB, which is well known for binding RNA and influencing which genes are turned “on” or “off” in a cell. To study the role of a protein like PTB, scientists often manipulate cells to reduce the amount of that protein, and then watch to see what happens. 

Several years ago, a postdoctoral researcher working in Fu’s lab was taking that approach, using a technique called siRNA to silence the PTB gene in connective tissue cells known as fibroblasts. But it’s a tedious process that needs to be performed over and over. He got tired of it and convinced Fu they should use a different technique to create a stable cell line that’s permanently lacking PTB. At first, the postdoc complained about that too, because it made the cells grow so slowly.

But then he noticed something odd after a couple of weeks — there were very few fibroblasts left. Almost the whole dish was instead filled with neurons.  

In this serendipitous way, the team discovered that inhibiting or deleting just a single gene, the gene that encodes PTB, transforms several types of mouse cells directly into neurons. 

More recently, Fu and Hao Qian, PhD, another postdoctoral researcher in his lab, took the finding a big step forward, applying it in what could one day be a new therapeutic approach for Parkinson’s disease and other neurodegenerative diseases. Just a single treatment to inhibit PTB in mice converted native astrocytes, star-shaped support cells of the brain, into neurons that produce the neurotransmitter dopamine. As a result, the mice’s Parkinson’s disease symptoms disappeared.

The study is published June 24, 2020 in Nature.

https://ucsdnews.ucsd.edu/pressrelease/one-time-treatment-generates-new-neurons-eliminates-parkinsons-disease-in-mice

3rd… From Out-Thinking … Eyes

2, 3, 4, 6 OPTIC NERVEOCULOMOTOR NERVE, TROCHLEAR NERVE , ABDUCENS NERVE 

  • Cranial Nerve 2 –  “a paired nerve that transmits visual information from the retina to the brain.” 
  • Cranial Nerve 3 – “supplies muscles that enable most movements of the eye and that raise the eyelid and enables the ability to focus on near objects as in reading.”
  • Cranial Nerve 4 – ” a motor nerve that supplies the superior oblique muscle” which controls turning of the eye in the socket, in particular the actions of looking down or towards the nose.
  • Cranial Nerve 6 – “a motor nerve that supplies the lateral rectus muscle of the eye” which controls turning of the eyes outwards, away from the nose.

……………………………….Since my being diagnosed with oblique double vision led me to finally receiving the diagnosis, I found it worthwhile to wade through the voluminous amount of goblty gook/geek speech. What I found fascinating was the reference to visual acuity, because back over 20 years ago I participated in something called applied kinesiology (muscle testing). Then a day came that I could no longer trust the answers I got. Various people came to the same conclusion… my polarity was reversed. Those same people told me how it could be made right. BUT traditional efforts failed to right my polarity. Then a doctor deduced… through muscle testing, that my problem was related to visual acuity. He said, “Whatever that is?” Twenty years later, I found the answer. So, does that mean the disease has been progressing in me for 20 years?

Eye and vision problems abound in Parkinson’s Disease, from dry eyes, involuntary closing of the eye lids, to fixed and unfocused eyes. Visual problems that have been strongly correlated with PD include issues with: visual acuity; contrast sensitivity; color vision; motion perception; visual disturbances and hallucinations. Physical and structural changes to the eye and retina have also been found in people with Parkinson’s, as determined by a number of modern eye examination methods. Therapies which involve injecting small amounts of dopamine into the eyeball have proven successful in PD, and strategies based on this are being developed”

After browsing 14 paragraphs of goblty gook… (from the link above… Eye and vision problems)

“Appreciation of the multiple sites of, for instance, contrast modulation is vital if we are to localize Parkinson’s disease-specific alterations in such processing to the anterior or posterior visual system.”

(and after another 7 large paragraphs of goblty gook) … “In other words, dopamine is a chemical messenger for light adaptation, promoting the flow of information through (neurons in the retina) cone circuits while diminishing that through rod circuits.”

(and after an additional 6 paragraphs of goblty gook) addressing Visual Acuity … “in generating a working hypothesis for the role of dopamine in the retina and the subsequent changes seen in Parkinson’s disease.”

(2 p goblty) “As temporal frequency increases, contrast becomes more difficult to perceive, resulting in flicker fusion, the point at which the stimulus appears not to change at all.”….. “Hence, at least from a retinal perspective, visual acuity and contrast sensitivity will depend not just on ‘optical’ factors … but also on ‘neural’ factors.” 

“There can be little doubt that dopaminergic deficiency plays an important role in retinal function, as seen in Parkinson’s disease.”…

Contrast sensitivity is vital for a range of day-to-day activities and diminished contrast sensitivity has been implicated in falls, difficulties in reading and driving performance, as well as with activities of daily living.” further more “Parkinson’s disease patients with visual hallucinations had significantly worse contrast sensitivity than those without hallucinations, suggesting a putative role for retinal dysfunction in the development of visual complications in Parkinson’s disease.”….

Deficits in colour vision in Parkinson’s disease are also well documented and suggest involvement of different colour-opponent pathways in the disease process.”….

“In addition to changes in visual acuity and contrast sensitivity, perception of motion is also affected in Parkinson’s disease.”…. “However, group differences persisted for measures of visual speed of processing and alternative measures of visual attention, supporting a cortical contribution to such perceptual disturbances as well.”…

In conclusion… “A better appreciation of how structural disease of the eye contributes to disability in Parkinson’s disease is overdue, particularly as effective treatments exist for many of the concomitant ocular disorders that may contribute to visual symptoms in Parkinson’s disease. Successful intervention therefore offers the prospect of improvements in the quality of life of Parkinson’s disease patients and their carers.”

Symptoms more than tremors

The url for this blog includes the phrase: silver linings and parkinsons so, I wanted to share a silver lining another Parkie typed:
“BTW, my tremor rocked an infant to sleep this week!”

 When I looked at this slide, I wondered… ‘What does ideopathic mean? …denoting any disease or condition or syndrome that arises spontaneously or for which the cause is unknown.

No photo description available.

The brain’s master chemical

This article about the brain’s master chemical, dopamine, is a little lengthy, but pretty informative and also gives ten natural ways to increase a person’s dopamine levels:

Christina Sarich, Guest in Waking Times

“Dopamine is the brain’s master chemical. This single neurotransmitter is responsible for a plethora of mental and physical processes. By learning how to stimulate your own dopamine levels naturally, you can overcome depression, anxiety, apathy, and fear, while boosting feelings of pleasure created by this amazing little neuron.”

“Dopamine is what rewards certain behaviors in us so that we do them again, and why certain drugs are so addictive. Cocaine, heroine and other opiates cause a dopamine “super reward”which makes their use highly desirable, until you experience the dopamine crash that comes once the illicit drug is absent from the physiology.”

“The opiates bind to the opiate receptors in the brain, increasing a dopamine release, but once gone, there is an ever-increasing need for more opiate (or other drug) to induce the same dopamine-high. This is what causes drug addicts to resort to ever increasing, negative behaviors to get their next “fix.” The dopamine high is that desirable.”

“In experiments conducted with mice, when the same nerve bundle that causes an opiate release was stimulated when they pressed a lever, the mice, left to their own devices, would press the lever thousands of times in an hour, due to the pleasurable feelings the dopamine would induce. A later experiment (conducted unethically on a human being) showed a similar response. Over the course of three hours, a person would press a button which triggered a dopamine dump thousands of times to get an immense emotional boost.”

“We get little dopamine dumps in our brains with less destructive behaviors – like making money, having sex, and even winning a video game, but there are dopamine boosting activities that can regularly boost our “pleasure” neurotransmitter, without causing an addictive backlash.”

“We have a certain number of dopamine neurons in the brain, and they are smaller than other neurons, making up less than 0.0006% of the neurons in the human brain, but we can stimulate the powerful nerve bundle in the brain that links dopamine neurons with their targets in the forebrain.”

“Dopamine does more than just boost our happiness quotient, though. It is also responsible for regulating our muscle movement, improving cognitive function, helping keep us focused, make decisions, evaluate problems and solve them, and regulating the secretion of prolactin.”

“Dopamine is undoubtedly, extremely important for our well being and happiness. Without high dopamine levels, we tend to experience depression, sadness, confusion, fear, negative thinking, rumination, and other emotional obstacles.”

“Following are some 100-percent-natural ways to increase your dopamine levels:”

Exercise

“Exercise elevates dopamine D2 receptors in the brain. It also happens to increase serotonin, and other endorphins in the body as well. Regular exercise can help prevent depression, reduce stress, and strengthen the mind just as much as it strengthens the body.”

Make a List and Cross Off the Things You Accomplish

“The brain dumps a little dopamine every time we successfully accomplish a task – no matter how big or small. To get even more dopamine “hits,” then break up big tasks into smaller pieces, and check them off one by one. This habit also has a tendency of keeping you moving toward your goals, and clearing the mental clutter in your mind.”

“The Principles of Self-Management state that if a task represents a change of 25% (or bigger change) in your life routine, you will feel disinclined to finish it, and often end up self-sabotaging or giving up. Conversely, making small changes (around 10%) keep you going in the right direction, and increase your pleasure.”

Eat Dopamine-Increasing Foods

“The essential amino acid, tyrosine is a precursor for dopamine. By eating foods that contain tryrosine, you can naturally boost dopamine levels. Find tryrosine in things like:

  • Eggs
  • Green tea
  • Milk
  • Watermelon
  • Coffee
  • Almonds
  • Bananas
  • Dark Chocolate
  • Yogurt”

Reduce Your Lipopolysaccharideds

“It’s a big word, but it is basically an endotoxin that causes your immune system to go berserk. Lipopolysaccharides also inhibit the production of dopamine.  By eating foods which protect the gut, such as yogurt, kefir, kimchi, and taking probiotics, you can lower your lipopolysaccharides, and allow dopamine to be created with ease.”

Detox

“While we’re on the topic of toxins, it is important to regularly detox. The accumulation of too many toxins in your body can prevent dopamine production. There are a myriad ways of detoxing, from green juicing, to taking activated charcoal, or doing a yogic master cleanse. The less toxic you are, the more super-charged your dopamine levels can get.”

Listen to Uplifting Music

“One of the easiest, and quickest ways to get a beneficial dopamine dump in the brain is from listening to music. Music creates “peak emotional moments” by making our brains “sing.”Music has been helping people feel uplifted since Paleolithic times. It’s that tried, and true.”

Get Creative

“It doesn’t matter if you express your creativity by doing arts and crafts, or writing an entire symphony, any creative activity increases levels of dopamine. Dance, take a figure drawing class, write a poem, cook something new, or even attack an auto-repair project with creative gusto, and you’ll be rewarded with higher dopamine levels.”

Start a Positive Streak

“Not only will this behavior increase dopamine levels, but it also happens to be the foundation for creating new, positive habits. See how many times you can do one new thing (like recycling your plastic or skipping soda) and mark it down on a calendar or tear sheet. See how long you can make the winning streak last.”

Supplement

“Dopamine levels can also be raised through supplementation. Try:

  • L-theanine increases numerous neurotransmitters in the brain, including dopamine. Green tea is a rich source of this plant compound.
  • Curcumin found prevalently in turmeric, effectively increases dopamine in the brain.
  • Ginkgo Biloba can raise dopamine levels.
  • Acetyl-l-tyrosine is a building block of dopamine, so a healthy dose of it supports the production of dopamine in the brain.”

Meditation and Yoga

“Meditation and yoga can effectively alter brain mechanisms that allow for bigger dopamine dumps. One of the reasons consistent meditators handle stress better, and usually feel good is due to an increase in GABA and dopamine. Meditation also releases us from the conditioned neural pathways which block the release of dopamine and other feel-good neurotransmitters.”