The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Restoring neural networks and understanding brain disorders

The Regenerative Neurophysiology Research Group
The Regenerative Neurophysiology Research Group – (left to right) Andreas Bruzelius, Daniella Ottosson (Prinicipal Investigator), Srisaiyini Kidnapillai, Christina-Anastasia Stamouli and Efrain Cepeda-Prado. Image credit: Johan Persson

A research group from Lund Stem Cell Center aims to understand a specific type of neuron that could underlie several brain disorders including schizophrenia, epilepsy and autism, and are developing exciting new strategies to treat them.

For the brain to function properly, signaling – be it excitatory or inhibitory – must be properly balanced. This is where a nerve cell known as interneurons come into play.

A specific type of interneuron that release the neurotransmitter gamma-aminobutyric acid (GABAergic interneurons for short) act as ‘brakes for the brain’, ensuring that this vital organ controlling all bodily functions is not overstimulated.

If these cells do not work properly, or are lost entirely, balance is disrupted – resulting in the development of neurodegenerative diseases and neuropsychiatric disorders.

“We want to understand why interneurons do not function in several brain disorders, such as schizophrenia and autism,” explains Daniella Ottosson - head of the Regenerative Neurophysiology research group at Lund University.

What role do interneurons play in brain diseases?
 

A major hurdle in the study of human interneurons has been the lack of availability of samples. To work around this, the research team make use of a powerful technique known as direct reprogramming. 

In one project, skin samples taken from patients with brain disorders are given specific signals, converting them directly into interneurons. “This allows us to generate human interneurons and study them outside of the brain,” continues Daniella.

 

Electrophysiology is used for assessing the neuronal function of the reprogrammed neuron. Image credit: Bengt Mattsson.
Electrophysiology is used for assessing the neuronal function of the reprogrammed neuron. Image credit: Bengt Mattsson.

Daniella’s team aim to identify key differences between ‘healthy’ interneurons and those from patients with brain disorders, specifically in how they function and connect.

Our goal is to establish different models in the lab that will give us a better understanding of the role interneurons play in the pathology of brain diseases,” explains Daniella.

Developing new strategies to treat brain disorders
 

There is currently no cure for brain disorders with underlying interneuron dysfunction – and their treatment can require a combination of medication with various types of therapy.

But what if you could replace lost or dysfunctional interneurons in brains and thereby restore the altered plasticity and networks characteristic of these disorders?

Daniella’s research group are focused on developing exciting new strategies to convert glial cells, a type of supportive cell found within the brain, into functional interneurons.

“To do this we inject specific transcription factors into the brain,” explains Daniella. “These factors are delivered by genetically modified viruses, which target glial cells and alter their gene expression patterns, converting them into interneurons.”

Using a technique known as electrophysiology – by which the researchers can investigate the electrical function of nerve cells – they are interested in how well the newly generated interneurons function, connect and integrate into the brain’s network, all necessary for a therapeutic effect. 

In the future, this type of therapy could be used to treat various brain disorders, by restoring the balance between excitation and inhibition signals in the brains of patients.

 

Immunofluorescence image of the mouse cortex showing several reprogrammed neurons (green) derived from glial cells. Red cells labels parvalbumin, an important GABAergic interneuron subtype. Image credit: Srisaiyini Kidnapillai
Immunofluorescence image of the mouse cortex showing several reprogrammed neurons (green) derived from glial cells. Red cells labels parvalbumin, an important GABAergic interneuron subtype. Image credit: Srisaiyini Kidnapillai

Importantly, glial cells have a regenerative capacity of their own, meaning that if a portion of them are converted into interneurons, the remaining cells will replace those missing converted cells. 

“We are currently focused on reprogramming glial cells to interneurons in mouse models, but if all goes to plan, we hope that this could in the future be a game changing new way of enhancing the life quality of sufferers of neurological disorders,” concludes Daniella.

A few weeks ago, the group published an exciting new study showing that human glia cells can also be reprogrammed into functional interneurons.

Direct Conversion of Human Stem Cell-Devived Glial Progenitor Cells into GABAergic Interneurons.


 

Daniella Ottosson. Image credit: Johan Persson
Daniella Ottosson. Image credit: Johan Persson

Daniella is a neuroscientist with a background in motor complications associated with Parkinson’s disease. Following a PhD with Prof. Angela Cenci Nilsson at Lund University, Daniella moved to Rome, Italy, for a postdoctoral training on synaptic integration after cell transplantation in Parkinson’s disease at the laboratory of Prof. Paolo Calabresi.

After her return to Lund 2013 she continued her research within field of Neural reprogramming and brain repair focusing on the functional assessment and synaptic contacts by newly generated neurons (Prof. Malin Parmar’s lab). Daniella here led her own research projects on in vivo neural reprogramming and established electrophysiology in this environment.

In 2017 Daniella received the Swedish Research Council Starting grant that enabled her to start her own research group currently consisting of one PhD student, two postdoctoral researchers and a Master’s student. Daniella Ottosson is a member of Lund Stem Cell Center and MultiPark.

Daniella Ottosson is funded by The Swedish Research Council, Jeanssons stiftelse, Hjärnfonden, Wenner-gren stiftelse, Per-Erik och Ulla Schyberg stiftelse, Åhléns-stiftelsen and the Royal Physiografic Society of Lund.

Contact details:
Daniella Ottosson

Associate Senior Lecturer
Principal Investigator
Regenerative Neurophysiology Group
Daniella [dot] ottosson [at] med [dot] lu [dot] se (Daniella[dot]Ottosson[at]med[dot]lu[dot]se)