New molecule could reverse neurodegeneration in Parkinson’s

 Author: Simge Eva Dogan        11 October 2018

Researchers at a university in Spain have discovered a new molecule which they claim can block and reverse neurodegeneration in Parkinson’s.

The molecule – named SynuClean-D – is able to reduce alpha-synuclein aggregations which cause degeneration.

The study – published in science journal ‘PNAS’ – explains how researchers at the Universitat Autònoma de Barcelona, Spain, tested over 14,000 molecules before discovering SynuClean-D.

They then tested the molecule on a Caenorhabditis worm – one of the most commonly used animals when researching neurodegenerative diseases – finding that it boosted its mobility and protected it from neural degeneration.

Salvador Ventura, the study coordinator, said: “Everything seems to indicate that the molecule we identified, the SynuClean-D, may provide therapeutic applications for the treatment of neurodegenerative diseases such as Parkinson’s in the future.”

The discovery of SynuClean-D

The researchers scanned over 14,000 molecules, looking for a specific feature: molecules that would be able to stop alpha-synuclein from sticking together into aggregates.

By employing novel methods of screening molecules and analyzing their properties, the scientists eventually identified SynuClean-D, which acts as an aggregation inhibitor.

In a further step, they also tested out the molecule in vitro, to see if it would be effective and safe to use in human neural cell cultures. Once this step was cleared, the team decided to also test SynuClean-D in vivo — in the Caenorhabditis elegans worm, which is often used in Parkinson's research.

C. elegans is a good model for Parkinson's because it expresses alpha-synuclein in the muscle or in certain nerve cells — namely dopaminergic neurons, which synthesize the key neurotransmitter dopamine.

These types of neurons are also involved in sending the messages that regulate mobility, so when their activity is inhibited by alpha-synuclein aggregates, an individual's ability to move is also impaired.

The scientists used two C. elegans models of Parkinson's disease in the current study. After administering SynuClean-D to the worms in food, the researchers found that it hindered alpha-synuclein from sticking together, protected the animals against neural degeneration, and boosted their mobility.

In the future, the researchers hope that their current findings will enable the development of more targeted treatments for neurodegenerative conditions.

"Everything seems to indicate that the molecule we identified, the SynuClean-D, may provide therapeutic applications for the treatment of neurodegenerative diseases such as Parkinson's in the future."

https://parkinsonslife.eu/new-molecule-reverse-neurodegeneration-parkinsons/#.W7-YVg8nwsc.facebook

FoxFeed Blog: New Law Seeks to Increase Access to Lower-cost Prescriptions

October 11, 2018

Stephanie Katz 

Recently, Congress and the administration took action on an issue that's top of mind for many people: access to affordable prescription drugs. Lawmakers passed two bills that allow pharmacists to tell people when they could save money by paying for their medications out-of-pocket rather than using health insurance. Previously, some pharmacists were barred from sharing this information.

This new rule applies to people who receive their health insurance through Medicare Part D, Medicare Advantage, private health plans and the exchange marketplaces. When you go to the pharmacy to fill your prescription, your pharmacist should provide you with the lowest price for your drug. If they do not offer this information, ask your pharmacist if the out-of-pocket price would be less than using your insurance. (Be sure to check with your pharmacist because savings will vary by prescription and by insurance plan.)

These bills, which were signed by the president on Wednesday, October 10, are the first pieces of legislation focused on prescription drug costs to become law since the administration released a proposal to tackle the high price of medications this past May.

The Michael J. Fox Foundation worked closely with Congress to secure the passage of these bills, sending several letters of support to senators and representatives so they could better understand the importance of this issue to the Parkinson's community.

The Foundation will continue to advocate in Washington to ensure patients have access to the care they need to manage their Parkinson's disease. Stay tuned to our blog for the latest updates on our public policy work and any news about efforts to lower drug prices.

https://www.michaeljfox.org/foundation/news-detail.php?new-law-seeks-to-increase-access-to-lower-cost-prescriptions

STUDY PROVIDES INSIGHTS ON THE EFFECTS OF EXERCISE ON COGNITIVE PERFORMANCE

NEUROSCIENCE NEWS    OCTOBER 12, 2018
Source: Wiley.

Study reveals both aerobic exercise and sitting in an upright posture improves visual working memory.

A new British Journal of Psychology study has looked at the details behind how cognitive performance may improve during aerobic exercise.

Electroencephalography readings were taken as 24 participants performed a visual working memory task while at rest and during exercise involving different postures: seated on or pedalling a stationary bicycle, as well as standing or walking on a treadmill. (Visual working memory is the ability to maintain visual information to serve the needs of ongoing tasks.)

The investigators found that both aerobic exercise and upright posture improved visual working memory compared with passive and seated conditions. Their analyses also suggest where the neural origins of these observed effects take place.

The investigators found that both aerobic exercise and upright posture improved visual working memory compared with passive and seated conditions. NeuroscienceNews.com image is in the public domain.

“Our findings hold implications not only for the field of cognitive psychology, wherein our knowledge has been primarily derived from seated, resting participants, but also for our understanding of cognitive performance at large. Although modern society has evolved to become more and more sedentary, our brains may nevertheless perform best while our bodies are active,” said lead author Dr. Thomas Töllner, of Ludwig-Maximilians-University Munich.

ABOUT THIS NEUROSCIENCE RESEARCH ARTICLE

Source: Penny Smith – Wiley

Publisher: Organized by NeuroscienceNews.com.

Image Source: NeuroscienceNews.com image is in the public domain.

Original Research: Open access research for “Electroencephalographic evidence for improved visual working memory performance during standing and exercise” by Gordon Dodwell, Hermann J. Müller, and Thomas Töllner in British Journal of Psychology. Published October 12 2018. doi:10.1111/bjop.12352

Abstract

Electroencephalographic evidence for improved visual working memory performance during standing and exercise

While a substantial body of research has investigated the effects of aerobic exercise on cognitive performance, few have monitored exercise‐concurrent cognitive processes via electroencephalography and fewer still using an event‐related potential (ERP) approach. As such, little is known regarding how the temporal dynamics of cognitive processing are influenced during aerobic activity. Here, we aimed to elucidate the influence of aerobic exercise on the temporal dynamics of concurrent visual working memory (VWM) performance. Participants performed a VWM retro‐cue task at rest and during aerobic exercise across two postural modalities: seated (using a stationary bicycle) and standing upright (using a treadmill). Three consecutive phases of the VWM processing pipeline were assessed by means of lateralized ERPs: access of VWM representations, response selection, and response execution. Aerobic exercise and upright posture were found to have significant effects on VWM performance, facilitating processing speed in the retro‐cue task. This facilitation arose primarily at an intermediary stage between the phases of accessing VWM representations and response selection. Our findings hold implications not only for understanding the influence of aerobic activity on VWM, but also for contemporary models of VWM that are built exclusively on data recorded during stationary, seated conditions.

https://neurosciencenews.com/exercise-cognitive-performance-10012/

Management Strategies for Later Stage Parkinson Disease

October 11, 2018  Caleb Rans, PharmD

• MDS Congress

CONFERENCE REPORTER

As one of the most prevalent movement disorders, Parkinson disease (PD) negatively affects patients and can have serious consequences. Both researchers and clinicians alike continue to search for improved treatment strategies to help patients manage the unique stages of the disease. Each year, the Movement Disorder Society (MDS) brings together the leading minds in movement disorder research.

The 2018 International Congress of Parkinson's Disease and Movement Disorders, which took place October 5 through 9 in Hong Kong, featured an update on management strategies for the later stages of PD, presented by Anthony Lang, MD, from the University of Toronto. In addition, several of the world’s brightest researchers presented their latest findings on the topic.

The transition from early to late stage PD is often characterized by severe motor disturbances and dyskinesia. Current management involves regularly increasing the number of levodopa administrations, in an attempt to prolong its activity at the neural synapse.¹ This can also be accomplished through the action of enzyme blockers and dopamine agonists.

However, this treatment strategy only remains effective for a short period of time, and as the disease progresses, patient mobility becomes increasingly restricted.

Management of late stage PD involves extending the therapeutic effect of levodopa, while lessening motor difficulties, which can include both drug infusion and invasive surgical techniques.² Additional drug therapies may be progressively added to a patient's regimen, including catechol-O-methyl transferase inhibitors, monoamine oxidase B inhibitors, and apomorphine. Newer enzyme inhibitor therapies include opicapone, safinamide, adenosine A2A receptor antagonists, and the levodopa/carbidopa intestinal gel infusion. More invasive interventions include both closed-loop and adaptive deep brain stimulation (DBS) and MRI-guided focused ultrasound.²

DBS is an effective surgical intervention for patients with advanced PD. In a recent quantitative, exploratory study presented at this year's Congress, researchers from the University College London investigated whether DBS met patient expectations post-surgery.³ The majority of study patients reported that their expectations after DBS were met (64% for motor symptoms; 71% for quality of life; 83% for reductions in medication daily dose) within 6 months to 2 years after surgery.³

"[DBS] did meet the perceived expected level of improvement in motor symptoms, [quality of life], and reduction in medication within 6 months to 2 years after surgery for the majority of patients which corresponded to the objective clinical outcome," the researchers wrote.

Another study at MDS explored patient experiences and attitudes surrounding earlier use of  DBS surgery.⁴ Using a structured interview format, investigators from Michigan State University found that 72% of study participants experienced high satisfaction post-DBS surgery.

These findings included both motor symptoms (mean 7.5/10) and quality of life improvements (mean 8.25/10). Moreover, they reported that on average, neurologists recommend DBS surgery about six years after initial PD diagnosis.4 However, patient opinions were mixed regarding whether or not they would have completed the procedure earlier.

"Our results suggest that while patients are grateful for improvements experienced with [ DBS], they generally did not endorse its implementation early in the disease progression," the researchers concluded.4

MRI-guided focused ultrasound is another emerging therapy that has shown evidence for the treatment of advanced PD.5 The technology allows for specific brain lesioning, accomplished via intracranial ablation. Surgical ablation has demonstrated improvements in certain symptoms of PD. As a result, the intervention is currently being studied for drug-resistant complications in select patients.

Urso and colleagues,6 a group of researchers from Móstoles, Spain, investigated the effects of MRI-guided focused ultrasound unilateral subthalamotomy on PD motor features assessed via electromyogram movement analysis. The researchers concluded stating that, "This study shows that [MRI-guided focused ultrasound] subthalamotomy improves [PD] motor features measured with [electromyogram] movement analysis.”

Another upcoming treatment area is in the development of novel device therapies, such as the levodopa/carbidopa intestinal gel infusion. A small case series suggested there may be additional benefit from infusion therapies in advanced PD.7

In the described case series, [PD] patients with advanced disease treated with [ DBS], had additional benefit from initiation of [levodopa/carbidopa intestinal gel] treatment. In an era of personalized medicine for [ PD] patients, combining advanced treatments can have a significant impact on patient’s symptoms and disability," the researchers wrote.7

Advanced PD remains a challenge for the practicing clinician. Balancing patient priorities and improving quality of life remain the main goals of therapy. Check back regularly with Neurology Timesto learn more about the latest advances in PD research.

Pages

References: 

1. Antonini A, Moro E, Godeiro C, Reichmann H. Medical and surgical management of advanced Parkinson's disease. Move Disord. 2018;33:900-908.

2. Antonini A, Nitu B. Apomorphine and levodopa infusion for motor fluctuations and dyskinesia in advanced Parkinson disease. J Neural Transm (Vienna). 2018;125:1131-1135.

3. Candelario-Mckeown J, Torkamani M, Sheridan H, et al. Does the degree of improvement after deep brain stimulation surgery for Parkinson’s disease (PD) meet the patient’s expectations? [abstract]. Mov Disord. 2018;33 (suppl 2). http://www.mdsabstracts.org/abstract/does-the-degree-of-improvement-after-deep-brain-stimulation-surgery-for-parkinsons-disease-pd-meet-the-patients-expectations. Accessed October 6, 2018.

4. Cabrera L, Sidiropoulos C. Attitudes toward earlier use of deep brain stimulation among patients with Parkinson’s disease [abstract]. Mov Disord. 2018;33 (suppl 2). http://www.mdsabstracts.org/abstract/attitudes-toward-earlier-use-of-deep-brain-stimulation-among-patients-with-parkinsons-disease. Accessed October 6, 2018.

5. Schlesinger I, Sinai A, Zaaroor M. MRI-Guided Focused Ultrasound in Parkinson's Disease: A Review. Parkinsons Dis. 2017;2017:8124624.

6. Urso D, Fernández-Rodríguez B, Rodríguez-Rojas R, et al. Effects of MRI-guided Focused Ultrasound unilateral subthalamotomy on characteristics of EMG activity underlying reaction time and tapping test in Parkinson’s disease [abstract]. Mov Disord. 2018;33 (suppl 2). http://www.mdsabstracts.org/abstract/effects-of-mri-guided-focused-ultrasound-unilateral-subthalamotomy-on-characteristics-of-emg-activity-underlying-reaction-time-and-tapping-test-in-parkinsons-disease. Accessed October 6, 2018.

7. Faust-Socher A, Yahalom G, Kestenbaum M, et al. Dual device aided therapy for patients with advanced Parkinson’s Disease: A case series [abstract]. Mov Disord. 2018;33 (suppl 2). http://www.mdsabstracts.org/abstract/dual-device-aided-therapy-for-patients-with-advanced-parkinsons-disease-a-case-series. Accessed October 6, 2018.

http://www.neurologytimes.com/mds-congress/management-strategies-later-stage-parkinson-disease/page/0/1

Spectramax Light Therapy Shows Promise in Easing Parkinson’s Non-motor Symptoms

OCTOBER 12, 2018 BY MARTA FIGUEIREDO IN NEWS.

PhotoPharmics’s Spectramax light therapy reduces disease severity, lessens non-motor symptoms, and improves the quality of life of Parkinson’s patients, according to recent results of a controlled clinical study.

The study,“Double-blind controlled trial of Spectramax™ light therapy for the treatment of Parkinson’s disease patients on stable dopaminergic therapy” was presented at the International Congress of Parkinson’s Disease and Movement Disorders (MDS), held Oct. 5-9, in Hong Kong, China.

Besides the well-known motor symptoms, Parkinson’s disease also is characterized by non-motor symptoms, such as cognitive impairment, sleep disturbances, depression, and pain.

These non-motor symptoms may occur years before Parkinson’s hallmark loss of dopamine-producing nerve cells and motor symptoms’ onset and usually are resistant to dopaminergic medications.

Parkinson’s patients also have a dysregulated circadian rhythm — the natural “body-clock” that regulates essential functions such as sleep, rest-activity rhythm, and metabolism — which has been increasingly associated with the development of the disease’s motor and non-motor symptoms.

Previous preclinical studies have suggested that light therapy improves the circadian rhythm and may be an effective therapy for both motor and non-motor features of Parkinson’s disease.

“Therapeutic light is the most powerful tool for circadian regulation, and based on our experience in treating circadian-related disorders with specific bandwidth phototherapy, we believe we can make a major difference in treating PD,” Dan Adams, PhotoPharmics’s science officer, said in a press release.

In the randomized, double-blind, clinical study (NCT02175472), PhotoPharmics evaluated the safety and effectiveness of Spectramax light therapy in Parkinson’s patients on stable dopaminergic therapy.

The trial enrolled 92 Parkinson’s patients 45 years or older at three centers in the U.S. and Europe. Participants were randomized to receive one hour of either light therapy (45 patients) or a placebo light (47 patients) every evening over six months. The placebo was a light therapy with a bandwidth that was not thought to be biologically active.

Patient’s disease severity (including motor and non-motor symptoms), sleep disturbances, anxiety, depression, and quality of life were assessed before and after six months of treatment through several validated methods.

According to PhotoPharmics’ website, the company’s Spectramax device, which provides strong but harmless doses of light in specific wavelengths, was mainly set on a table or desk at the participants’ home. This way, patients were able to do several activities — such as read, watch TV, and eat a meal — while receiving the light therapy.

After six months of light therapy, patients showed a clinically meaningful improvement on disease severity — assessed through the Movement Disorders Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) — compared with patients in the placebo group.

Treated patients also showed a significant reduction in non-motor symptoms (measured through Part 1 of the MDS-UPDRS), a significant improvement in their quality of life (assessed using the Parkinson’s Disease Questionnaire (PDQ-39)), and an almost statistically significant reduction in daytime sleepiness (measured through the Epworth Sleepiness Scale), compared with those receiving only standard dopaminergic treatment.

Spectramax light therapy was well-tolerated, with dry eye, teary eye, and eye strain being the most common side effects.

These results are a “significant milestone for patients with Parkinson’s disease and showcases what may be the only adjunctive therapy to improve Parkinson’s disease symptoms on top of the dopaminergic medications that patients are likely already taking,” said Kent Savage, PhotoPharmics’ CEO.

PhotoPharmics noted that larger double-blind studies are required to confirm these results, and that the company plans to conduct additional clinical trials to further investigate light therapy in neurodegenerative diseases

https://parkinsonsnewstoday.com/2018/10/12/spectramax-light-therapy-shows-promise-in-easing-parkinsons-non-motor-symptoms/

Deep Fatigue Is More than Tiredness

OCTOBER 12, 2018  DR. C'S JOURNEY WITH PD 

Fatigue is a symptom commonly associated with Parkinson’s disease (PD) and one I experience more often each year. The term “fatigue” alone does not do justice to the experience. It is too easy to relate fatigue to being tired or overworked, or to muscle aches after hard physical labor. I have had those experiences and none of them compare to PD-related fatigue. I’ve needed a new way to define this different level of fatigue. Thus, I have adopted the term “deep fatigue.”

Deep fatigue is different in its intensity and its incorporation of nonmotor symptoms. Deep fatigue involves every muscle, sometimes even involuntary ones. They are all tired and weak, and in my case, also in pain. If I have been exercising, then those muscles groups will have a higher level of pain. In deep fatigue, it is common for me to have pain levels at six or seven. (I associate level seven with spontaneous tears.) At the same time, emotions become much more intense, almost overwhelming, and difficult to manage. Mental energy is used to manage the pain and the emotions, leaving little energy for anything else.

My duration of deep fatigue is slowly increasing each year. Presently, my deep fatigue lasts between one to six hours. It’s like dragging a ball and chain during those hours.

These things seem to make deep fatigue worse:

• Exercising too hard or too long
• Eating too much animal protein, or too big a meal
• Not resting when needed
• Getting overheated and not hydrating
• Being overly stressed
• Being sick with a virus
• Missing a levodopa dose

Obviously, avoiding the above is part of my rehab plan for dealing with deep fatigue. Rest and sleep are VERY important.

I am a very active person, but deep fatigue must be addressed with rest. Taking a day to rest is not in my nature. It makes me feel like a sloth. Yet, when deep fatigue hits me, the best remedy is to do just that — take the day off! I limit myself to one day of physical rest, very rarely two days (usually following some stressful event). I also find that the mind must rest with the body. Getting the mind to a quiet place is the practice of meditation, in whatever form suits the moment. At the height of deep fatigue, meditation can be very difficult, but not impossible. At times, it has taken me four hours to quiet my mind and body to get rejuvenating rest.

(Graphic by Dr. C)

But there is a caution here: Be wary of using rest as an excuse to procrastinate. In another column, I’ll address the link of scenario looping to set-shifting issues and difficulty initiating new tasks. Basically, getting off the sofa can be problematic if I stay there too long. Perhaps this seems contradictory to my history as a highly active person, but that is the nature of PD’s nonmotor effects. Once off the sofa, I make myself shift into a physical task, followed by a short rest and then some type of mental task. There is always some resistance to overcome to do this — to get off the sofa — but the rest is absolutely necessary to stop the deep fatigue.

***

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.

https://parkinsonsnewstoday.com/2018/10/12/parkinsons-disease-deep-fatigue-more-than-tiredness/

Study: Ketogenic diet appears to prevent cognitive decline in mice

October 12, 2018, University of Kentucky

PET scan of a human brain with Alzheimer's disease. Credit: public domain

We've all experienced a "gut feeling"—when we know deep down inside that something is true. That phenomenon and others (like "butterflies in the stomach") aptly describe what scientists have now demonstrated: that the gut and the brain are more closely connected than we once thought, and in fact the health of one can affect the other.

Capitalizing on this relatively new scientific concept, Ai-Ling Lin and her colleagues at the Sanders-Brown Center on Aging at the University of Kentucky have published two studies that demonstrate the effect of diet on cognitive health in animals.

The first, in Scientific Reports, demonstrated that neurovascular function improved in mice who followed a Ketogenic Diet regimen.

"Neurovascular integrity, including cerebral blood flow and blood-brain barrier function, plays a major role in cognitive ability," Lin said. "Recent science has suggested that neurovascular integrity might be regulated by the bacteria in the gut, so we set out to see whether the Ketogenic Diet enhanced brain vascular function and reduced neurodegeneration risk in young healthy mice."

Lin et al considered The Ketogenic Diet—characterized by high levels of fat and low levels of carbohydrates—a good candidate for the study, as it has previously shown positive effects for patients with other neurological disorders, including epilepsy, Parkinson's disease, and autism. Two groups of nine mice, aged 12-14 weeks, were given either the Ketogenic Diet (KD) or a regular diet. After 16 weeks, Lin et al saw that the KD mice had significant increases in cerebral blood flow, improved balance in the microbiome in the gut, lower blood glucose levels and body weight, and a beneficial increase in the process that clears amyloid-beta from the brain—a hallmark of Alzheimer's disease.

"While diet modifications, the Ketogenic Diet in particular, has demonstrated effectiveness in treating certain diseases, we chose to test healthy young mice using diet as a potential preventative measure," Lin said. "We were delighted to see that we might indeed be able to use diet to mitigate risk for Alzheimer's disease."

According to Lin, the beneficial effects seen from the Ketogenic Diet are potentially due to the inhibition of a nutrient sensor called mTOR (mechanistic target of rapamycin), which has shown to effect lifespan extension and health promotion. In addition to the Ketogenic Diet, Lin said, mTOR can also be inhibited by simple caloric restriction or the pharmaceutical rapamycin.

The second study, published in Frontiers in Aging Neuroscience, used neuroimaging techniques to explore in vivo the effects of rapamycin, the Ketogenic Diet, or simple caloric restriction on the cognitive function of both young and aging mice.

"Our earlier work already demonstrated the positive effect rapamycin and caloric restriction had on neurovascular function," Lin said. "We speculated that neuroimaging might allow us to see those changes in the living brain."

Even more tantalizing: her data suggested that caloric restriction functioned as a sort of "fountain of youth" for aging rodents, whose neurovascular and metabolic functions were better than those of young mice on an unrestricted diet.

Lin emphasizes that it's too early to know whether the regimens will confer the same benefit in humans, but since rapamycin and other mTOR inhibitors have already been approved by the FDA and are widely prescribed for other diseases, it's realistic to think that study in humans could follow relatively quickly.

Linda Van Eldik, Ph.D., Director of the UK Sanders-Brown Center on Aging, said that Lin's work justifies a transition to similar studies in humans, since all of the methods Lin used in animal models can be readily applied to humans.

"Ai-Ling's lab was the first to use neuroimaging to see these changes in a living brain, and the potential link to changes in the gut microbiome," she said. "Her work has tremendous implications for future clinical trials of neurological disorders in aging populations."

Lin and her lab are already doing just that; designing a clinical trial to understand the role of the gut microbiome in neurovascular dysfunction (a risk factor for AD) and in healthy aging.

"We will use neuroimaging to identify the association between gut microbiome balance and brain vascular function in individuals over 50 years of age, with an ultimate goal to design and test nutritional and pharmacological interventions that will prevent Alzheimer's disease," she said.

More information: Jennifer Lee et al, Neuroimaging Biomarkers of mTOR Inhibition on Vascular and Metabolic Functions in Aging Brain and Alzheimer's Disease, Frontiers in Aging Neuroscience (2018).  DOI: 10.3389/fnagi.2018.00225

Journal reference: Scientific Report

Provided by: University of Kentucky

https://medicalxpress.com/news/2018-10-ketogenic-diet-cognitive-decline-mice.html

Human brain cell transplant offers insights into neurological conditions

October 11, 2018, Imperial College London

Transplanted human brain cells (green) and nuclei (purple). Credit: R Real, et al. Science 2018

In the new study, led by Imperial College London in collaboration with a group from the University of Cambridge, researchers transplanted human brain cells into a mouse brain, and for the first time watched how they grew and connected to each other. This allowed the team to study the way human brain cells interact in a more natural environment than previously possible.

The team, funded by the Medical Research Council, used the technique to model Down syndrome, using cells donated by two individuals with the condition.

The scientists say their approach could be used to study a range of brain conditions in the future, including schizophrenia, dementia or autism. 

The study, published today in the journal Science, describes how researchers saw differences in the brain cells from the individuals with Down syndrome compared to brain cells from a person without the condition.

Although some of the connections formed between the brain cells from the individuals with Down syndrome were more stable and abundant, they communicated in a slightly less coordinated fashion.

Dr. Vincenzo De Paola, lead author of the research from Imperial's Institute of Clinical Sciences, said: "It's been a fantastic team effort and I'm grateful to the many scientists who participated in this study, as well as to the people who donated tissue samples for this research. Our results suggest the reduced coordinated activity and increased stability of connections in Down syndrome may be linked to cognitive function. Figuring this out would be an important piece of the puzzle, and we hope to have an answer soon."

Professor Rick Livesey, joint co-corresponding author from the University of Cambridge's Wellcome/Cancer Research UK Gurdon Institute, commented: "Working together with the Imperial team has allowed us to extend our previous work on making stem cells and nerve cells from people with Down syndrome, to study how those nerve cells develop and function when put in a living brain. We are very excited by how much we have learned and the new avenues this has opened up for understanding Down syndrome".

Dr. Raquel Real, a neurologist from Dr. De Paola's group at Imperial College London and joint first author of this study, added: "The transplantation of human brain cells has allowed us to monitor their maturation over time. Ultimately, we detected that cells from Down syndrome individuals are not as active as normal cells at a crucial stage in their development, and this could have important implications for some of the symptoms of this condition".

Dr. De Paola added: "Scientists have been struggling to develop a way of monitoring live human cells and their connections in the brain. This new imaging approach may have taken us one step closer to this."

Crucially, the technique allows scientists to study how brain cells communicate, explained Dr. De Paola: "The connections between brain cells, which enable them to talk to each other, is often the first thing to be damaged in conditions such as dementia and Parkinson's. This happens long before the brain cells themselves start to die. But the connections are so tiny, that no type of scanning tool available, such as MRI or PET scans, can see them. 

We used a revolutionary microscopy technique—called in vivo 2-photon microscopy—which allowed us to see not only individual live brain cells, but also the connections between them."

In the study, joint first author Dr. Manuel Peter and colleagues from the Gurdon Institute created human brain cells by reverse-engineering skin cells. This process involved taking a few skin cells from volunteers with Down syndrome, and then reprogramming them in the lab to form brain cells. They then engineered those neurons so their activity could be monitored.

Joint first authors Dr. Raquel Real and Dr. Antonio Trabalza from the Imperial College London group were then able to implant these human neurons in the brain of live mice and monitored their development and function over time.

Dr. De Paola explained: "The human brain cells not only formed complex networks, but also started communicating in a way that was very similar to normal brain cells. We were hoping a few of the human brain cells would grow within the mouse brain—but we were stunned to see the human brain cells thrive, and soon talk and work together."

However, he cautioned: "It is still not clear to what extent the transplanted human brain cells resemble the organization and complexity of their counterparts in the human brain. We now need to investigate this with further experiments."

The Imperial team now hope to refine this technique, and potentially use this approach to study other neurological conditions.

More information: R. Real el al., "In vivo modeling of human neuron dynamics and Down syndrome," Science (2018). science.sciencemag.org/lookup/ … 1126/science.aau1810

Journal reference: Science

Provided by: Imperial College London

https://medicalxpress.com/news/2018-10-human-brain-cell-transplant-insights.html