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Astrocytes identified as master ‘conductors’ of the brain

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In the orchestra of the brain, the firing of each neuron is controlled by two notes – excitatory and inhibitory – that come from two distinct forms of a cellular structure called synapses.

Synapses are essentially the connections between neurons, transmitting information from one cell to the other. The synaptic harmonies come together to create the most exquisite music–at least most of the time.

When the music becomes discordant and a person is diagnosed with a brain disease, scientists typically look to the synapses between neurons to determine what went wrong. But a new study from Duke University neuroscientists suggests that it would be more useful to look at the white-gloved conductor of the orchestra – the astrocyte.

Astrocytes are star-shaped cells that form the glue-like framework of the brain. They are one kind of cell called glia, which is Greek for “glue.” Previously found to be involved in controlling excitatory synapses, a team of Duke scientists also found that astrocytes are involved in regulating inhibitory synapses by binding to neurons through an adhesion molecule called NrCAM. The astrocytes reach out thin, fine tentacles to the inhibitory synapse, and when they touch, the adhesion is formed by NrCAM. Their findings were published in Nature on November 11.

“We really discovered that the astrocytes are the conductors that orchestrate the notes that make up the music of the brain,” said Scott Soderling, PhD, chair of the Department of Cell Biology in the School of Medicine and senior author on the paper.

Excitatory synapses — the brain’s accelerator — and inhibitory synapses — the brain’s brakes — were previously thought to be the most important instruments in the brain. Too much excitation can lead to epilepsy, too much inhibition can lead to schizophrenia, and an imbalance either way can lead to autism.

However, this study shows that astrocytes are running the show in overall brain function, and could be important targets for brain therapies, said co-senior author Cagla Eroglu, PhD, associate professor of cell biology and neurobiology in the School of Medicine. Eroglu is a world expert in astrocytes and her lab discovered how astrocytes send their tentacles and connect to synapses in 2017.

“A lot of the time, studies that investigate molecular aspects of brain development and disease study gene function or molecular function in neurons, or they only consider neurons to be the primary cells that are affected,” said Eroglu. “However, here we were able to show that by simply changing the interaction between astrocytes and neurons — specifically by manipulating the astrocytes — we were able to dramatically alter the wiring of the neurons as well.”

Soderling and Eroglu collaborate often scientifically, and they hashed out the plan for the project over coffee and pastries. The plan was to apply a proteomic method developed in Soderling’s lab that was further developed by his postdoctoral associate Tetsuya Takano, who is the paper’s lead author.

Takano designed a new method that allowed scientists to use a virus to insert an enzyme into the brain of a mouse that labeled the proteins connecting astrocytes and neurons. Once tagged with this label, the scientists could pluck the tagged proteins from the brain tissue and use Duke’s mass spectrometry facility to identify the adhesion molecule NrCAM.

Then, Takano teamed up with Katie Baldwin, a postdoctoral associate in Eroglu’s lab, to run assays to determine how the adhesion molecule NrCAM plays a role in the connection between astrocyte and inhibitory synapses. Together the labs discovered NrCAM was a missing link that controlled how astrocytes influence inhibitory synapses, demonstrating they influence all of the ‘notes’ of the brain.

“We were very lucky that we had really cooperative team members,” said Eroglu. “They worked very hard and they were open to crazy ideas. I would call this a crazy idea.”

Insight

How housing design can improve quality of life

Richard Grota, director of Edward Architecture, discusses how design and adaptation of homes can be vital to physical and mental wellbeing

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Housing should be designed for all forms of disability. Some people who are regarded as disabled are in fact largely disabled by their environment and can become trapped in their own homes or spaces living a life restricted by poor design. 

It is critical that these people get the access to resources to give them a way of using their space that provides the very best quality of life.

In the UK, there are more than 13 million people living with a disability which comes in many guises such as physical, sensory and mental illnesses. It is becoming increasingly important to create architectural design that provides freedom of movement for all. 

Varied needs require a varied design solution which can be adapted to suit different physical restrictions. Architecture is all about human comfort and in the words of The Commission for Architecture and the Built Environment, ‘by improving the quality of buildings and spaces, this will have a lasting influence on the quality of people’s lives’.

Anyone who creates a custom-made property has the opportunity to really think about what they need from their home, both now and in the future, and to take all crucial and desired elements into account. 

For those who have a disability, the opportunity to adapt their house or create a new tailor-made dwelling could dramatically improve their daily life and bring families closer together. 

It can be an emotional process working with people and listening to how the things most people take for granted, such as interaction with their children, have become an impossible challenge due to the physical environment they are living in.

Designs need to support developers and the people that they serve, both for their physical and mental health, and there are so many ways to achieve this. Through thoughtful design and by working closely with people, we can get to the heart of the changes that would be life altering. 

Sometimes it is the smallest change that can make the biggest difference, for example, viewing the garden from someone’s bed, or the incorporation of a larger window to a small room and really listening to people when they explain how they want their space to function to accommodate the daily routines of themselves and their family members. 

Central living space is often key to enabling free movement around core areas and everyone will use their homes in different ways. For some, it’s all about being able to do meal and bath times with their children with ease. For others, the incorporation of sensory rooms is life-changing, and these can take all forms depending on what elements are important for the individual. 

Accessible design goes far beyond just making a home wheelchair-friendly, and there is a real stir in the market at the moment towards designing dwellings that can be stylish and modern. 

Flexible homes can be designed without knowing they are for a particular need and without compromise on style. A well-designed space with a specific practical purpose will enhance rather than inhibit design. 

The architect’s role is to design, specify and oversee building projects from inception through to completion, ensuring that schemes meet the needs of the individual and the recommendations and rehabilitation programmes made by their professional advisors. Designs must always have the full approval of the client, their occupational therapists, case managers, solicitors and all other relevant parties prior to works commencing, to ensure the completed works are exactly as requested. 

With the current climate, many people are spending more time in the home than ever, both as a result of the ongoing fears around COVID-19 and as a knock-on effect of the rise in working from home. 

Wellness as a concept has never been so important. A growing body of evidence is demonstrating how the design of buildings, streets, parks and neighbourhoods can support good physical and mental health, help reduce health inequalities and improve people’s wellbeing by building healthy experiences into people’s everyday lives. 

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Insight

The power of music

Ana Pessoa, a music therapist at Renovo Care Group, reflects on the life-changing impact of music

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“What does music mean to me?” was one of the first pieces of written reflection I produced when I trained to become a Music Therapist.

I revisited the document where I wrote about the significance of music in my life and career choices, and I realised I did not really deepened the concept of meaning per se (maybe I will not here either…). At the time I did not know better, psychodynamically speaking, or perhaps, I was just not ready to see the bigger picture but also the detail within it.

I did write about and reflected on my first “therapeutic” musical experience, one that I hold close to my heart. I had a very close friend, a grandmother figure, who often took me to the beach to play by the sea and to pick up shells. She shared the beauty and immensity of the sea with me as well as the way she perceived its myriad of sounds, scents and shades. In our outings she would sing a Portuguese traditional song that, little did I know, would be an everlasting bond between us.

O mar enrola na areia (The sea curls onto the sand)

Ninguém sabe o que ele diz (Nobody knows what it says)

Bate na areia e desmaia (Hits the sand and faints)

Porque se sente feliz (Because it [the sea] feels blissful)

Ana Pessoa

When, ten years later, she was diagnosed with Alzheimer’s disease, this song seemed to calm her down, even when she no longer had the ability to communicate verbally. Every time I gently sang the “sea song”, she would smile and sometimes drop a tear. To this day I wonder what she was feeling or remembering. I was 17 and it was the first time I truly understood the power of music.

“Our” song became a form of communication between us through the very last stage of the disease until she passed away. Aldridge states that “when the body is failing… the soul requires another form of contact” (Aldridge, 2001, p. 22) and that is exactly what music did for her. I will forever be grateful for having had the privilege of being the medium for that connection to happen, even though at the time I did not fully understand it.

I have recently lost a dear friend and musical mentor who played a big part in shaping who I am. Olga Prats was, without a doubt, my musical compass and, despite our age difference which did not really matter, Olga was my confidant of all things, a brilliantly generous pianist and, quite possibly, the biggest chamber music reference in Portugal. She was a skilled and tactful pianist with a fantastic ability to bring instruments together, letting each and every single one of them shine, but also support each other in a harmonious way. Olga’s piano playing was so present, so mindful that it was an experience in itself.

It was not until after her passing that I revisited the meaning of music: what does it mean to me, Ana the woman, Ana the pianist, Ana the therapist, and equality important, what does music mean to my patients. 

I have quickly realised that psychodynamic Music Therapy, one of the approaches I practice, is much like chamber music. If there is a lack of attention to detail in the parts, the whole simply does not work. I made the connection between therapy and chamber music because if I, as a therapist, do not treat a patient taking into account all aspects of their being and their lived experience, therapy will most likely not be effective.

There are patients that are not particularly fond of music, so providing music therapy without understanding, in the first place, why are they not fond of music is, arguably, a futile exercise. Therefore, similarly to what I would do if I were to play in a chamber music ensemble where I would read and play all the parts before the first rehearsal, I start by creating a safe space for the patient to express what they are feeling “now”, exploring as far back as they are willing to.

Working with an acquired brain injury population, these feelings often come in the form of frustration, sadness, despair, loss of identity and hopelessness. The process of learning the parts and matching them to a particular sound, timbre or rhythm are profoundly meaningful, both for the patient and for myself as their therapist. Comparably to the process of rehearsing different melodic and harmonic parts, each therapy session feels as though we are putting the pieces of a puzzle together, and, in a magnificent way, Olga’s teachings that were focused on three grand musical aspects, skill, meaning and sharing, permeate and live through the way I exist as a therapist and the way I see and perceive the meaning of music played in my sessions. 

I now realise how profound and complex this subject of musical meaning is. Although I still relate with the words I wrote on my first year of training, where music meant, and still means, devotion, care, survival, alliance, faith and freedom, joy and pleasure, generosity and love in their purest forms, I have also come to the realisation that music is the tool that allows patients to navigate through darkness, despair and their very personal “storms”. 

And, in a neurologic music therapy perspective, music is the key to light up the whole brain like a Christmas tree birthing new neuro pathways and creating the possibility of rewiring the injured brain. Music is a common ground for lifelong connections like that which I shared with Olga. 

So, thank you music for inspiring me in my naivety, for being there for me as I grew. Thank you for challenging me, and for making me question and reflect. Thank you for comforting me in difficult moments, for accompanying me in my success, thank you for giving my patients hope, and for framing lasting memories. 

Rest peacefully Olga, my forever “music mother”.

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Insight

‘I’d love for my voice to be heard’

Alarna Simmons, assistant psychologist at Renovo Care, looks at the importance of reflective exercises with patients

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A lot of times in our day to day interactions with patients they share with us their worries and concerns.

We guide them through the rehabilitation process reassuring them and offering not just physical support but also emotional support as they come to terms with life changing experience.

But how often do we stop and really ask the patient to tell us their perspective in its entirety? I mean beyond the initial gathering of social history for context or the questions from various assessments.

I wanted to provide a patient with the opportunity to do just that. Not only does the interview below serve as a really good reflective exercise contributing to the patients’ goal, but it is also a means of their voice being heard.

I hope this encourages other staff who work with patients in rehab or another setting, and also to other patients who are at different points in their recovery journey, may it inspire you to keep going!

Can you tell me about how you were in the early stages of your diagnosis?

“I was really scared that I would be paralysed forever. I would always think ‘will I ever walk again?’.

“I was happy until I got ill. I felt really depressed and suicidal. I thought I won’t have much of a life if I am paralysed forever.

“Everyday my emotions were very up and down. Sometimes I would feel okay and other times I would be really depressed. It could change really quickly.

“At first, I was positive I would get better but then after a relapse I felt hopeless and it was hard to be positive after that. I used to be very anxious all the time, constantly in pain, and I did not trust people”. 

How are things for you now?

“Most of the time I wake up feeling positive and like I have a purpose but sometimes the negative thoughts come. I tell myself its not true and it’s good that I recognise it is happening now and I can stop it.

“When I achieve things especially in physio it makes the negative thoughts go away and I feel like I am stronger that I thought. I have learnt ways to be calm and now I feel like I can trust the people around me. I don’t care how long my recovery takes it will be worth it”.  

What are some of the things that have helped you mentally?

  • Relaxation has helped me to be much calmer, especially now my pain is under control
  • Being able to talk to staff about my feelings and not feel judged has helped me a lot
  • Positive affirmations that I say everyday like “I am good enough” “I am strong” “I am not useless” “I can do it” and “I believe in myself because I can get better” have helped to remind me every day. Sometimes I will repeat over and over “do it for [my son]” 
  • Being able to phone my mum helps me a lot. Before I used to self-harm but now, I can talk to my mum instead 
  • Seeing my own progress has helped me to believe in myself and makes me feel like I can get better. It also lets me know that the negative thoughts are not true. 

Based on the difference what would you say to your past self if you could?

“I would say to be patient and stop getting angry at yourself for not being able to do physio because you will be able to do it later when the pain is under control. Try to be more positive and stop thinking negative things like “I’m not going to get better” because its not true”. 

What inspires you?

“I feel inspired when staff tell me about previous patient who had the same condition as me and was doing really well when they left here. It lets me know that it is possible, and I hope me sharing this will help another person”. 

What do you hope for in the future?

“I hope that I can walk again. My favourite place is the beach, so I want to be able to go there with my son and nephews and play in the water.

“I want to be able to use my hands as well to feed myself. I want to be happy all the time and not get stuck on negative things. I know I might still have some negative thoughts (as everyone does) but I will be able to let them go by without them affecting me.

“I want to feel like a proper mum to my son again and do more things with my family like quality time”. 

What would you say to another patient?

“Keep going, and don’t give up, I never thought I would get this far”. 

What would you say to other therapists or hospital staff?

“It is important to know the patients’ condition, be understanding and patient with them. I also like staff who are motivating, encourage me and believe in me”. 

My hope is that if anyone else completes a reflective exercise with a patient that they will offer praise for not just the transparency but the bravery that comes with sharing their experience.

It is an absolute joy of mine to see the progress of our patients and conversations like the one above just reinforce the fact that as a team we are truly making a difference.

At Renovo Care, we place high importance on our values of person-centred working, effective teamwork, respect, dignity, integrity, open and honest communication, and providing an environment of learning and development for staff, patients and therapists alike. 

Encouraging our patients from the beginning to take one step and one day at a time and being with them for each of these steps, celebrating the highs and lows of the rehabilitation journey is an honour and the reason for waking up in the morning and going to work with a joyful heart. 

 

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