"With this new finding, we can now generate in a dish the neuronal misfiring that is similar to what occurs in the brain of a Parkinson's patient," said Feng. Credit: Douglas Levere, University at Buffalo
Abnormal
oscillations in neurons that control movement, which likely cause the tremors
that characterize Parkinson's disease, have long been reported in patients with
the disease. Now, University at Buffalo researchers working with stem cells
report that they have reproduced these oscillations in a petri dish, paving the
way for much faster ways to screen for new treatments or even a cure for
Parkinson's disease.
The
paper is published online today (May 2) in Cell Reports.
"With
this new finding, we can now generate in a dish the neuronal misfiring that is
similar to what occurs in the brain of a Parkinson's patient," said Jian
Feng, PhD, senior author on the paper and professor in the Department of
Physiology and Biophysics in the Jacobs School of Medicine and Biomedical
Sciences at UB. "A variety of studies and drug discovery efforts can be
implemented on these human neurons to speed up the discovery of a cure for
Parkinson's disease."
The
work provides a useful platform for better understanding the molecular
mechanisms at work in the disease, he added.
Rhythmic
bursts
Abnormal
brain oscillations first came to light decades ago when some Parkinson's
patients began undergoing deep brain
stimulation as treatment once their medications ceased to be
effective. Neurosurgeons doing the procedure noticed rhythmic bursts of
activity or oscillations among neurons in patients when they used electrodes to
override brain activity in order to stimulate the brain.
"Our
bodies move because there is coordination between the contracting and relaxing
of our muscles," explained Feng. "It's all exquisitely timed within
the brain structure called basal ganglia."
The
rhythmic bursts of activity or oscillations that neurosurgeons saw in the
brains of Parkinson's patients signaled that something in that system had
broken down but exactly how wasn't clear.
Neuronal
nonsense
Feng
and his colleagues generated induced pluripotent stem cells (iPSCs) from
the skin cells of patients with mutations in the parkin gene. Years earlier,
Feng's team had used the same technology to discover that these mutations cause
Parkinson's disease by disrupting the actions of dopamine, which is necessary
for normal physical movement. When there isn't enough dopamine, an imbalance in
neurotransmission occurs, ultimately resulting in Parkinson's disease.
"What
we found in our new research is pretty dramatic," he said. "When we
recorded electrical activity in the neurons with parkin mutations, you could
clearly see the oscillations."
The
mutations induce a change in how neurons communicate, Feng said.
"Normally,
communication between these neurons is not repetitive," he said, "but
in this case, we suspect that the oscillation reduces the information content
being transmitted. It's almost like stuttering, as though now the neuron can't
understand the instructions for normal movement. All the neurons 'hear' is
nonsense."
To
make sure that the oscillations were caused by parkin mutations, the
researchers then used a virus to rescue the mutations. With normal parkin back
in the neuron, the oscillations disappeared.
Potential
drugs
"This
research gives us a very nice way to screen for drugs because the phenotype is
very much like what is going on in the brain," Feng said.
"Whatever blocks the oscillation
in the dish could be a potential drug
candidate." This idea led to discussions with Q-State Biosciences, a
startup developed by Harvard University professors Adam E. Cohen, PhD, and
Kevin Eggan, PhD, that focuses on stem cell and optogenetic technologies.
Feng
noted that the UB research was extremely tedious. The neurons had to be cultured
for more than 100 days and the medium needed to be changed every two days.
Q-State Biosciences is interested in developing a high-throughput technique,
which would be highly valuable to pharmaceutical companies that want to quickly
screen potential drug candidates for Parkinson's disease.
Journal reference: Cell Reports
Provided by: University at Buffalo
https://medicalxpress.com/news/2017-05-parkinson-dish-brain-oscillations.html
No comments:
Post a Comment