A midbrain organoid in a petri dish. The black pigment is neuromelanin, a hallmark of the human midbrain. Credit: Agency for Science, Technology and Research (A*STAR), Singapore
Scientists
in Singapore have made a big leap on research on the 'mini-brain'. These
advanced mini versions of the human midbrain will help researchers develop
treatments and conduct other studies into Parkinson's Disease (PD) and
ageing-related brain diseases.
These
mini midbrain versions are three-dimensional miniature tissues that are grown
in the laboratory and they have certain properties of specific parts of the
human brains. This is the first time that the black pigment neuromelanin has
been detected in an organoid model. The study also revealed functionally active
dopaminergic neurons.
The
human midbrain, which is the information superhighway, controls auditory, eye
movements, vision and body movements. It contains special dopaminergic neurons
that produce dopamine - which carries out significant roles in executive
functions, motor control, motivation, reinforcement, and reward. High levels of
dopamine elevate motor activity and impulsive behaviour, whereas low levels of
dopamine lead to slowed reactions and disorders like PD, which is characterised
by stiffness and difficulties in initiating movements.
Also
causing PD is the dramatic reduction in neuromelanin production, leading to the
degenerative condition of patients, which includes tremors and impaired motor
skills. This creation is a key breakthrough for studies in PD, which affects an
estimated seven to 10 million people worldwide. Furthermore, there are people
who are affected by other causes of parkinsonism. Researchers now have access
to the material that is affected in the disease itself, and different types of
studies can be conducted in the laboratory instead of through simulations or on
animals. Using stem cells, scientists have grown pieces of tissue, known as
brain organoids, measuring about 2 to 3 mm long. These organoids contain the
necessary hallmarks of the human midbrain, which are dopaminergic
neurons and neuromelanin.
Differentiation of human embryonic stem cells in a step wise protocol into human midbrain organoids that contain neuromelanin. Credit: Agency for Science, Technology and Research (A*STAR), Singapore
Jointly
led by Prof Ng Huck Hui from A*STAR's Genome Institute of Singapore (GIS) and
Assistant Prof Shawn Je from Duke-NUS Medical School, this collaborative
research between GIS, Duke-NUS, and the National Neuroscience Institute (NNI)
is funded by the National Medical Research Council's Translational Clinical
Research (TCR) Programme In Parkinson's disease (PD) and A*STAR. Other
collaborators are from the Lieber Institute for Brain Development, the Johns
Hopkins University School of Medicine, and the Nanyang Technological
University.J
Assistant
Prof Shawn Je from Duke-NUS Medical School's Neuroscience & Behavioural
Disorders Programme said, "It is remarkable that our midbrain organoids
mimic human midbrain development. The cells divide, cluster together in layers,
and become electrically and chemically active in three-dimensional environment
like our brain. Now we can really test how these mini brains react to existing
or newly developed drugs before treating patients, which will be a game changer
for drug development."
Prof
Tan Eng King, Research Director and Senior Consultant, Department of Neurology
at NNI and Lead PI of the TCR Programme in PD, remarked, "The human brain
is arguably the most complex organ and chronic brain diseases pose considerable
challenges to doctors and patients. This achievement by our Singapore team
represents an initial but momentous scientific landmark as we continue to
strive for better therapies for our patients."
GIS
Executive Director Prof Ng Huck Hui said, "Considering one of the biggest
challenges we face in PD research is the lack of accessibility to the human
brains, we have achieved a significant step forward. The midbrain organoids
display great potential in replacing animals' brains which are currently used
in research; we can now use these midbrains in culture instead to advance our
understanding and future studies for the disease, and perhaps even other
related diseases."
Midbrain organoids, measuring about 3 mm across, cultured in the laboratory dish. Note the black pigments are neuromelanin. Credit: Agency for Science, Technology and Research (A*STAR), Singapore
Journal reference: Cell Stem Cell
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