There are two types of
neurons in the brain: excitatory and inhibitory neurons. They do exactly what you think they
would. Excitatory neurons release
chemical messengers, which activate other neurons, which may eventually lead to
some sort of perception or action.
Inhibitory neurons release chemicals that silence other neurons. Why would you want inhibitory neurons in your
brain? Well, if all your neurons were
excitatory and interconnected, all your neurons would be active all the time
and the signals would be meaningless. In
fact, this sort of overactivation in the brain can lead to seizures. It’s been shown in numerous cases of epilepsy
that there is some sort of dysfunction of the inhibitory neurons. The excitatory neurons have free reign and go
crazy, leading to a seizure.
How is epilepsy
treated? Medications that potentiate the
inhibitory neurons can help, but they activate all inhibitory neurons
throughout the brain, when maybe the problem is more localized to one spot. Just as all excitatory neurons is a bad
thing, too much inhibition is also bad and can lead to cognitive side
effects. Another treatment is to open up
the patient’s head, try to find the overactive area and cut it out or zap those
neurons with a laser. Destroying brain
cells is always a last resort, though.
In a recent paper published
in Nature Neuroscience by Hunt et al., the authors propose another potential
treatment: adding new inhibitory neurons into the epileptic brain. Like all new medical ideas, the story starts
with mice. They can create a model of
human epilepsy in these mice by treating them with a potent drug. These epileptic mice have seizures just like
humans do.
Where do you get new
inhibitory neurons?
The researchers obtained
progenitor cells from mice embryos. In
other words, these weren’t inhibitory neurons yet, but they were destined to
turn into them as the mice developed.
They grafted these progenitors into adult epileptic mice in the
hippocampal region of the brain (a common area for seizures). Amazingly, these pre-neurons migrated
throughout the brain region, as far as 1.5 mm (that’s a lot… think about how
small a mouse brain is). Then the
progenitors differentiated into inhibitory neurons, as if they were in a normal
developing brain. One week later, the
epileptic mice with extra inhibitory neurons had hardly any seizures, whereas
the untreated mice were having about 2 a day.
Not only that, but the treated mice showed cognitive improvements
compared to the untreated epileptic mice.
So they seemed to “cure” the
epileptic mice by giving them some new inhibitory neurons that were able to
make functional connections with the existing neurons. This isn’t as invasive as brain surgery and
it’s much more localized than medication.
If the epilepsy were focused in a different part of the brain, then they
could transplant the cells there instead.
Is this possible to try in
humans? Maybe so, but the first problem
is that we can’t take inhibitory progenitor cells from human embryos. There are some ethical issues with growing
clones to harvest parts from them.
However, you could use embryonic stem cells, or induced pluripotent stem
cells. Pluri-what? Recent technology allows researchers to take
a skin biopsy, do some genetic engineering to these cells and push them back in
developmental time to a stem cell.
Pluripotent means that these stem cells have the potential to become any
type of cell, like an inhibitory neuron.
All it takes is turning on the right genes in these cells to push them
to a particular fate, and if that isn’t already known for inhibitory neurons, I
bet it’s not too far off. Plus there’s
the benefit that the transplanted cells will have the same genome as all the
patient’s other cells, because they originated from their skin cells. Just wait, regenerative medicine is moving ahead
at lightning speed.
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