Most of us take for granted the voluntary
control we have over our bodies.
If you want to wave at someone, you simply
think of moving your arm, and you wave.
Pretty trivial, right?
However, these actions are controlled by a
very complex network inside our brain.
It makes sense that damage to this network
would lead to difficulty in performing voluntary
movements, which is the main sign of a neurodegenerative disease
called Parkinson’s disease.
In order to understand how Parkinson’s disease
affects voluntary movement, we must first
understand the machinery of the nervous system.
Our brain and nerves are made up of cells
called neurons which form a vast network.
Let’s zoom into one of these connections
between two neurons, called a synapse.
When a signal moves down a neuron, that neuron
will release chemical messengers called neurotransmitters
into the synapse.
These neurotransmitters can bind to receptors
on the next neuron to excite it, allowing
the signal to continue on.
Release of a different neurotransmitter or
binding to a different receptor can instead
cause inhibition of the next neuron, preventing
the signal from continuing.
Neurons are therefore either excitatory or
inhibitory depending on whether they cause
the next neuron to turn on or off.
Different patterns of excitatory and inhibitory
neurons allow all kinds of messages to be
relayed from one part of the body to another.
Three important areas of the brain are involved
in voluntary movement: the motor cortex, the
basal ganglia, and the thalamus.
These three areas are connected by inhibitory
and excitatory neurons, which are shown as
red or green arrows.
Each arrow represents many similar neurons
grouped together.
When we want to move, the motor cortex sends
a signal to the basal ganglia.
The basal ganglia regulate movement by either
activating or inactivating the inhibitory
neurons between the basal ganglia and the
thalamus.
If these inhibitory neurons are activated,
the neurons connecting the thalamus to the
motor cortex are not allowed to send signals.
If those neurons do not fire, the motor cortex
receives no feedback, and no movement occurs.
Conversely, if these inhibitory neurons are
inactivated, then nothing is stopping the
neurons connecting the thalamus and motor
cortex from being excited, so they activate
the motor cortex.
The motor cortex then sends signals down the
spine
to cause certain parts of the body to move.
Therefore, the basal ganglia essentially decide
whether or not movement is allowed.
How do the basal ganglia actually make their
decision?
Two distinct pathways of neurons within the
basal ganglia can be activated, which for
simplicity’s sake, is shown by two arrows.
In reality, they are actually composed of
a combination
of excitatory and inhibitory neurons.
If the direct pathway is activated, the inhibitory
neurons connecting the basal ganglia and the thalamus
are inactivated, and movement occurs.
If the indirect pathway is activated, the
inhibitory neurons are activated,
and movement is prevented.
In fact, the indirect pathway is constantly
activated, allowing you to stay still at rest.
When you want to move your body, you want
the indirect pathway to stop being activated
and the direct pathway to be activated.
The release of a neurotransmitter called dopamine
by neurons originating from an area of the
basal ganglia called the substantia nigra
can both activate the direct pathway and inactivate
the indirect pathway, initiating movement.
This is because dopamine can bind to D1 receptors
in the starting neuron of the direct pathway
to activate it, as well as binding to D2 receptors
in the starting neuron of the indirect pathway
to inactivate it.
This is just a taste of how complex the neuroscience
in our brain is. One neurotransmitter can
cause both excitatory and inhibitory effects
just by binding to different receptors!
In healthy people, these dopaminergic neurons
slowly die out as age increases, but in people
with Parkinson’s, this decrease is dramatically
accelerated.
Scientists don’t really know why these neurons
die out, but brain autopsies show that within
those neurons, there are clumps of proteins
called Lewy bodies.
Are these Lewy bodies deadly to neurons?
Or are they simply a result of some other
unknown source of damage?
Research is still going on to determine their
function.
One thing is for sure though – without dopamine,
initiating movement becomes extremely difficult,
leading to two of the three common symptoms
of Parkinson’s: bradykinesia and rigidity.
These in turn lead to other motor problems
such as speech, writing, and balance difficulties.
The third and most well-known symptom, resting
tremors, is not completely explained by the
death of dopaminergic neurons. New research
shows that other parts of the brain such as
the cerebellum, as well as other neurotransmitters
such as serotonin, play a role in this symptom.
Around 30% of people with Parkinson’s do
not develop this uncontrollable shaking at
the start, but most eventually develop it
as the disease progresses.
Strangely enough, these people also end up
suffering from more severe Parkinsonian symptoms.
Why is this?
One possible hypothesis is that tremors actually
make initiating movement easier by keeping
the muscles in constant motion, decreasing
the effects of bradykinesia and rigidity.
Therefore, developing tremors early may serve
as a protective function.
It’s also important to note that not all
symptoms are expressed to the same extent
between different people.
As time progresses, other areas of the brain
become damaged as well, leading to slowed
thought, memory loss, poor problem solving,
and depression.
All of these symptoms make life very challenging
for both the patients and their caregivers.
However, Parkinson’s disease itself is not
lethal.
Lack of dopamine will not directly kill you.
Instead, most patients will die from accidents
caused by the symptoms, such as choking or
falling, or blood clots from lack of movement.
With proper and loving care, these risks can
be avoided and people with Parkinson’s can
have a normal life expectancy.
Parkinson’s mostly affects the elderly aged
50 or older, with approximately 1% of all
seniors having this disease.
Approximately 10% of cases develop
before age 50, known as early-onset Parkinson’s.
Around 10 million people are affected worldwide,
with men almost 50% more likely to be affected than women.
Research has shown that exposure to certain
pesticides or having many family members with
Parkinson’s seem to increase the risk of
developing the disease, implying that both
environmental and genetic factors play a role.
However, this only describes a minority of
people with Parkinson’s, with the majority
being cases with no known cause.
No such cure that reverses the damage to dopaminergic
neurons has been found.
However, since Parkinson’s disease is due
to a lack of dopamine, it makes sense that
treating this disease would involve increasing
dopamine levels.
Dopamine is naturally broken down in the synapse
by enzymes, so prolonging its time in the
synapse can indirectly increase its effect.
This can be done by drugs that inhibit enzymes
that break down dopamine.
Other drugs can directly increase dopamine
levels, such as levodopa which can be converted
into dopamine in the body, and dopamine agonists,
which are similar in structure to dopamine
and can bind to dopamine receptors.
All of these drugs are effective at first,
but eventually stop working or lead to many
side effects.
One day, as scientists have more and more
understanding of how the disease progresses,
a permanent cure may be found.
To speed up that process, or to learn more
about Parkinson’s disease, check out some
of the websites posted in the description
below to see how you can help.
Thanks for watching, and see you next time
for another explanation of a disease on Medicurio.
