Nav: Home

New ways to mass produce human neurons for studying neuropsychiatric disorders

August 04, 2016

Scientists from Singapore have streamlined the process of using human stem cells to mass produce GABAergic neurons (GNs) in the laboratory. This new protocol provides scientists with a robust source of GNs to study many psychiatric and neurological disorders such as autism, schizophrenia, and epilepsy, which are thought to develop at least in part due to GN dysfunction.

GNs are inhibitory neurons that reduce neuronal activation, and make up roughly 20 per cent of the human brain. They work alongside excitatory neurons (ENs) to ensure balanced neural activity for normal brain function. The coordinated interplay between GNs and ENs orchestrate specific activation patterns in the brain, which are responsible for our behaviour, emotions, and higher reasoning. Functional impairment of GNs results in imbalanced neural activity, thereby contributing to the symptoms observed in many psychiatric disorders.

The availability of high quality, functional human GN populations would facilitate the development of good models for studying psychiatric disorders, as well as for screening drug effects on specific populations of neurons. Scientists worldwide have been hard at work trying to generate a consistent supply of GNs in the laboratory, but have been faced with many challenges. Protocols involving multiple complex stages, poor yield, and requiring a long time to generate mature and functional GNs are just some of the limitations encountered.

Many of these limitations have now been overcome by the development of a rapid and robust protocol to generate GNs from human pluripotent stem cells (hPSCs) in a single step. With the addition of a specific combination of factors, hPSCs turn into mature and functional GNs in a mere six -- eight weeks. This is about two -- three times faster than the 10 - 30 weeks required for previous protocols. In addition, this new protocol is highly efficient, with GNs making up more than 80 per cent of the final neuron population.

To develop this protocol, the team from Duke-NUS Medical School (Duke-NUS), A*STAR's Genome Institute of Singapore (GIS) and the National Neuroscience Institute (NNI) first identified genetic factors involved in GN development in the brain. The team then tried many different combinations of these factors, and succeeded in confirming that mature and functional human GNs were indeed generated.

"Just like how a balance of Yin and Yang is needed in order to stay healthy, a balance of ENs and GNs is required for normal brain function. We now know a fair bit about ENs because we have good protocols to make them. However, we still know very little of the other player, the GNs, because current protocols do not work well. Yet, when these GNs malfunction our brain goes haywire," commented Dr Alfred Sun, a Research Fellow at NNI and co-first author of the publication alongside Mr Qiang Yuan, an NUS Graduate School PhD student.

"Our quick, efficient and easy way to mass produce GNs for lab use is a game changer for neuroscience and drug discovery. With increased recognition of the essential role of GNs in almost all neurological and psychiatric diseases, we envisage our new method to be widely used to advance research and drug screening," said Dr Shawn Je, Assistant Professor in the Neuroscience and Behavioural Disorders Programme at Duke-NUS, and senior author of the study.

The speed and efficiency of generating GNs with this new protocol provides researchers unprecedented access to the quantities of neurons necessary for studying the role of GNs in disease mechanisms. Drugs and small molecules may now be screened at an unparalleled rate to discover the next blockbuster treatment for autism, schizophrenia, and epilepsy.
-end-
Published on 4 August 2016 in Cell Reports, this research is supported by the Singapore National Research Foundation under its Cooperative Basic Research Grant, administered by the Singapore Ministry of Health's National Medical Research Council (NMRC/CBRG/0075/2014), the Ministry of Education, Singapore (MOE2012-T2-1-021, MOE2014-T2-071), A*STAR Biomedical Research Council (13/1/96/19/688), and a Duke-NUS Signature Research Programme Block Grant.

Summary of key findings:
  • A new protocol has streamlined the process of using human pluripotent stem cells to mass produce GABAergic neurons (GNs) in the laboratory in a single step.
  • The GNs produced from this protocol not only bear the identifying markers, but also behave and function similarly to GNs found in the brain.
  • Generating GNs would allow scientists to develop better models of psychiatric disorders to be studied in the laboratory, while also rapidly screening drugs.


Duke-NUS Medical School

Related Schizophrenia Articles:

Dietary supplement may help with schizophrenia
A dietary supplement, sarcosine, may help with schizophrenia as part of a holistic approach complementing antipsychotic medication, according to a UCL researcher.
Schizophrenia: Adolescence is the game-changer
Schizophrenia may be related to the deletion syndrome. However, not everyone who has the syndrome necessarily develops psychotic symptoms.
Study suggests overdiagnosis of schizophrenia
In a small study of patients referred to the Johns Hopkins Early Psychosis Intervention Clinic (EPIC), Johns Hopkins Medicine researchers report that about half the people referred to the clinic with a schizophrenia diagnosis didn't actually have schizophrenia.
The ways of wisdom in schizophrenia
Researchers at UC San Diego School of Medicine report that persons with schizophrenia scored lower on a wisdom assessment than non-psychiatric comparison participants, but that there was considerable variability in levels of wisdom, and those with higher scores displayed fewer psychotic symptoms.
Recognizing the uniqueness of different individuals with schizophrenia
Individuals diagnosed with schizophrenia differ greatly from one another. Researchers from Radboud university medical center, along with colleagues from England and Norway, have demonstrated that very few identical brain differences are shared amongst different patients.
Resynchronizing neurons to erase schizophrenia
Today, a decisive step in understanding schizophrenia has been taken.
Genetics researchers close in on schizophrenia
Researchers at the MRC Centre for Neuropsychiatric Genetics and Genomics at Cardiff University have discovered 50 new gene regions that increase the risk of developing schizophrenia.
Looking for the origins of schizophrenia
Schizophrenia may be related to neurodevelopment changes, including brain's inability to create the appropriate vascular system, according to new study resulted from a partnership between the D'Or Institute for Research and Education, the University of Chile and the Federal University of Rio de Janeiro (UFRJ).
Researchers uncover novel mechanism behind schizophrenia
An international team of researchers led by a Case Western Reserve University School of Medicine scientist has uncovered a novel mechanism in which a protein--neuregulin 3--controls how key neurotransmitters are released in the brain during schizophrenia.
A new genetic marker for schizophrenia
Japanese scientists find a rare genetic variant that shows strong association with schizophrenia.
More Schizophrenia News and Schizophrenia Current Events

Top Science Podcasts

We have hand picked the top science podcasts of 2019.
Now Playing: TED Radio Hour

In & Out Of Love
We think of love as a mysterious, unknowable force. Something that happens to us. But what if we could control it? This hour, TED speakers on whether we can decide to fall in — and out of — love. Guests include writer Mandy Len Catron, biological anthropologist Helen Fisher, musician Dessa, One Love CEO Katie Hood, and psychologist Guy Winch.
Now Playing: Science for the People

#542 Climate Doomsday
Have you heard? Climate change. We did it. And it's bad. It's going to be worse. We are already suffering the effects of it in many ways. How should we TALK about the dangers we are facing, though? Should we get people good and scared? Or give them hope? Or both? Host Bethany Brookshire talks with David Wallace-Wells and Sheril Kirschenbaum to find out. This episode is hosted by Bethany Brookshire, science writer from Science News. Related links: Why Climate Disasters Might Not Boost Public Engagement on Climate Change on The New York Times by Andrew Revkin The other kind...
Now Playing: Radiolab

An Announcement from Radiolab