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Gene linked to long lifespans can protect from stress

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"Without SAM, lamin can't form this strong barrier and DNA starts leaking out."

A gene linked to unusually long lifespans in humans protects brain stem cells from the harmful effects of stress, a new study has found.

Studies of humans who live longer than 100 years have shown that many share an unusual version of a gene called Forkhead box protein O3 (FOXO3).

That discovery led Dr Jihye Paik, associate professor of pathology and laboratory medicine at Weill Cornell Medicine, and her colleagues to investigate how this gene contributes to brain health during ageing.

In 2018, Dr Paik and her team showed that mice who lack the FOXO3 gene in their brain are unable to cope with stressful conditions in the brain, which leads to the progressive death of brain cells.

And their new study reveals that FOXO3 preserves the brain’s ability to regenerate by preventing stem cells from dividing until the environment will support the new cells’ survival.

Stem cells produce new brain cells, which are essential for learning and memory throughout our adult lives,” says Dr Paik.

“If stem cells divide without control, they get depleted. The FOXO3 gene appears to do its job by stopping the stem cells from dividing until after the stress has passed.”

Many challenges like inflammation, radiation or a lack of adequate nutrients can stress the brain. But Dr Paik and her colleagues looked specifically what happens when brain stem cells are exposed to oxidative stress, which occurs when harmful types of oxygen build up in the body.

“We learned that the FOXO3 protein is directly modified by oxidative stress,” she says.

This modification sends the protein into the nucleus of the stem cell where it turns on stress response genes.

The resulting stress response leads to the depletion of a nutrient called s-adenosylmethionine (SAM). This nutrient is needed to help a protein called lamin form a protective envelope around the DNA in the nucleus of the stem cell.

“Without SAM, lamin can’t form this strong barrier and DNA starts leaking out,” she says.

The cell mistakes this DNA for a virus infection, which triggers an immune response called the type-I interferon response. This causes the stem cell to go dormant and stop producing new neurons.

“This response is actually very good for the stem cells because the outside environment is not ideal for newly born neurons,” Dr Paik continues.

“If new cells were made in such stressful conditions they would be killed. It’s better for stem cells to remain dormant and wait until the stress is gone to produce neurons.”

The study may help explain why certain versions of the FOXO3 are linked to extraordinarily long and healthy lives – they may help people keep a good reserve of brain stem cells.

It may also help explain why regular exercise, which boosts FOXO3 helps preserve mental sharpness.

But Dr Paik cautions it is too early to know whether this new information could be used to create new therapies for brain diseases.

“It could be a double-edged sword,” Dr Paik adds.

“Over activating FOXO3 could be very harmful. We don’t want to keep this on all the time.”

To better understand the processes involved, she and her colleagues will continue to study how FOXO3 is regulated and whether briefly turning it on or off would be beneficial for health.

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New company launched to drive forward Parkinson’s research

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Up to £800,000 will be invested over the next two years

Charity Parkinson’s UK is to launch a new company dedicated to driving forward research into Parkinson’s disease.

Vivifi Biotech has been created to lead and plan preparations for a new trial into the role of the restorative protein glial cell-derived neurotrophic factor (GDNF) in Parkinson’s.

Launched through the charity’s drug development arm, Parkinson’s Virtual Biotech, up to £800,000 will be invested over the next two years as efforts continue to find a life-changing new treatment for people living with the disease.

Plans for a new trial build on the initial groundbreaking clinical investigations in GDNF, the results of which proved inconclusive but did show some signs that the treatment may have started to regenerate participants’ dopamine-producing brain cells.

“The unwavering passion and determination of the GDNF participant group has ensured that the potential of GDNF, and the role of patients in research, has never been forgotten,” says Paul Jackson Clark, director of engagement at Parkinson’s UK.

“They’ve tirelessly campaigned, fundraised and shared their experience with us, enabling us all to get to this monumental point.

“We now have the chance to see if we can find a life-changing new treatment that people with Parkinson’s desperately need. There are still plenty of obstacles but this announcement gives us the opportunity to move things forward together.”

Parkinson’s UK was the major funder of the initial trial, which investigated whether boosting levels of GDNF could slow, stop or reverse the progression of Parkinson’s.

Tom Phipps was a participant in the GDNF trial.

“My outcome was as positive as I could have wished for, I feel the trial brought me some time and has delayed the progress of my condition,” he says.

“The trial participants have always believed in GDNF’s potential,” said Parkinson’s UK in their announcement.

“So have we and the other organisations involved in the trial.

“Some participants tell us they’re still experiencing the benefits, years on from undergoing this experimental therapy. We’ve been working with them since the end of the trial.

“Together, we want to make sure we’ve explored every option.”

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Community rehab

Music group launched to support BAME community

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Leicester Musical Memory Box is launching its online music project Geet Sangeet

A music group established to support people living with dementia, memory loss and brain injury has received funding to launch an online project for the South Asian and BAME community.

Leicester Musical Memory Box (LMMBox) was founded in July 2018, and since that time has grown from one group in the city to six, providing interactive music sessions for people of all ages and backgrounds, including a group specific to the South Asian community.

The group – which has two staff members who are fluent in Gujarati, Hindi, Punjabi and Urdu – aims to provide the local community with a supportive network and a safe space to explore the unique challenges that a brain injury may bring to individuals, as well as their families and carers.

The new online music project is named ‘Geet Sangeet’ – translated as ‘Songs Sung Together’ – and will incorporate music and cultural references specific to the South Asian community, led by group leader Beena Masand from LMMBox.

Each session will begin with gentle exercises to warm up the body and brain, followed by singing and discussion about various music, songs, and media.

Attendees will also receive their own ‘musical memory box’ in a bag to help increase the interactivity of the sessions.

The project has received funding from the new Local Connections Fund, and is in collaboration with Headway Leicester.

Music has proven benefits for people with memory problems or a brain injury, including enabling people to connect with past experience and enabling freedom of expression, confidence and independence.

Attendance at the groups also helps to improve mood and reduce feelings of social isolation.

“We know we are providing a vital service to our members and receive enquiries regularly,” says Kyle Newman, group leader and co-director of LMMBox.

“In spite of the lockdown, we are thrilled to be able to once again provide a culturally specific group for the South Asian community.

“We also know that the group leader needs to come from that community and have the music and cultural knowledge to be able to engage participants effectively.”

“We are delighted to collaborate with LMMBox and reach out to more people across Leicester who have been affected by brain injury,” adds Mary Goulty, service manager at Headway Leicester.

“There is a clear need for a support service within the BAME community and that’s why we launched our BAME group last year, which is providing a vital lifeline to brain injury survivors we support and their families.”

To contact LMMBox, visit www.leicestermusicalmemorybox.co.uk

For support with brain injury in the Leicester community, visit www.headwayleicester.org.uk.

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Art Therapy offers an emotional outlet for those living with a Traumatic Brain Injury (TBI)

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Masks not only allow us to hide our true feelings but to also express them without fear of judgement.

Being able to ‘hide’ one’s true self, may be a way, for others, to truly ‘show’ themselves.

For this reason, Chroma therapists began delivering Art Therapy sessions online to those living with a Traumatic Brain Injury (TBI) in an attempt to help them express their emotions in a creative, non-threatening way.

A TBI can have devastating effects upon a person’s mental health, as well as physical, with emotional issues caused by significant, sudden changes in appearance and abilities.

Studies have found Art Therapy to be effective in helping TBI patients with emotional expression, socialisation, emotional adaptation to mental and physical disabilities, and communication in a creative and non-threatening way.1

Self-expression is fundamental in processing the effects of a TBI. Take a look at the image below.

On the left is the base mask. During the process of art therapy, across a number of sessions, the participant talks, reflects and begins to create ideas or metaphors which then get placed onto the base mask. Often this depicts the face he presents to the outside world, in contrast with the dual parts of to his inner personality including a bright peaceful side and a dark, tumultuous side.

Based on the sessions, Chroma therapists are better able to gauge the patient’s feelings, discuss the final piece and help the patient begin to process their emotions.

In effect, art therapy offers a creative gateway to communication and used in this way, tries to enable the participant to externalise their inner thoughts and feelings.

As a therapy, it has been shown to help reduce feelings of stress, promote creativity and imagination as well as increase self-expression, confidence and communication.

Chroma began delivering these sessions as a way to allow clients to reveal thoughts and feelings about themselves which they may find hard to express, or may not even be aware of, and which may be being expressed through more difficult behaviours.

They also create an opportunity for greater communication, allowing therapists to gain a deeper understanding of the client’s thoughts, anxieties and feelings.

Being able to express themselves creatively helps the client reveal their true feelings, which in itself can be cathartic – a relief to release their emotions, in a personal, safe space.

Chroma continues to deliver these sessions online to help reach as many TBI sufferers across the UK as possible in an attempt to help them begin to process their emotions concerning the effects the TBI had upon them, with the outlook to help improve their mental wellbeing which in turn will help promote a positive outlook to life and rehabilitation outcomes.

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