Putting it all together – Pathophysiology of Parkinson’s disease | NCLEX-RN | Khan Academy
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Putting it all together – Pathophysiology of Parkinson’s disease | NCLEX-RN | Khan Academy


– [Voiceover] So we know
that Parkinson’s disease causes problems with movements right? And what we see in people
with Parkinson’s disease is a reduction, a loss, a
slowing down of movements. And this happens largely because of a loss of dopamine neurons in the brain. But, you might be wondering, “What is so special about
these dopamine neurons?” “How do they actually cause
these problems with movements?” “What’s going on here?” And that’s actually a
really great question. So let’s have a look at
how that all happens. So let’s start off by jumping over here to the substantia nigra. And you might remember this, that the substania nigra is the
main area in the brain where we see this big loss
of dopamine neurons, right? So we have these dopamine neurons here, in the substantia nigra,
so they head over, they project to the striatum. So let’s draw some of
these, so here’s some dopamine neurons here
in the substantia nigra. And they go over here to the striatum. So they send their axions over here, and they go and they talk
to neurons in the striatum. And we actually have
a name for this little bundle of dopamine neurons, this little highway that goes from the substantia nigra to the striatum. And we call it the
“nigrostriatal pathway.” Nigro, because they head
from the substantia nigra, and striatal, because they
head over to the striatum. So, during Parkinson’s
disease, these neurons, they start to die off, right? We start to lose some of these neurons. And actually, this is really interesting. So as these neurons are starting to die, as we’re starting to lose the neurons in Parkinson’s disease, what we also see, at the same time, is
this formation of these little clumps of proteins
in a lot of these neurons. And these are called “Lewy bodies.” And these Lewy bodies start to form, and we’re not gonna go into the kind of, the pathological diagnosis
of Parkinson’s disease at this point, but in what
we call a “post mortem exam,” so after the person has died and we’re looking at their brain, these
Lewy bodies are actually the main thing that we
see in the brains of people with Parkinson’s disease. And the really interesting
part, is the we actually don’t know at this point
what role Lewy bodies play in the disease. We don’t know if they’re, maybe involved in the loss of these dopamine neurons, or maybe if they’re actually like a protective mechanism, to kind of, try to prevent more loss
of dopamine neurons, or maybe something that we haven’t even thought about yet. We just, we don’t know at this point. And so that’s kind of a
interesting bit of research that’s currently going on. So anyway, so back to our
nigrostriatal pathway here. So more and more of these
dopamine neurons die. We lose more of them,
and when we’ve lost about about 80% of them, so quite a bit right? 80%, that’s when we start
to see bradykinesia, and rigidity, and some
problems with movements. The things that are
actually the physical signs of Parkinson’s disease. So in order to figure out how this loss of dopamine neurons actually leads to the movement problems that we see, we have to kind of
think back to the direct and the indirect pathways
that the basal ganglia in our brains use to
control our movements. So I like to think of
the thalamus as a dog, a dog on a leash. And it needs to be on a leash because we don’t want it getting all excited. Because when the thalamus
gets all excited, it causes our motor
cortex to get too excited. And this causes our
muscles to move too much, too much movement. Because remember, our
motor cortex is what talks to our muscles to get them to move. So we keep our thalamus
on a tight leash, right? So this is what we do. And we do this so it can’t
over-excite the motor cortex. And the basal ganglia, their job is to adjust the length of our leash. And this adjusts how
active the thalamus can be. And they do this by talking to each other in the direct and the indirect pathways. So the aim of the direct pathway is to loosen our leash on the thalamus. To let our thalamus be
a bit more active and chat with our motor cortex more, so that we can move around a bit more. So let’s say maybe you’re
crossing the street, and the light is about to change. And, you know you’re a good person, you don’t wanna hold up traffic. So you need to go from walking to running, in order to make sure that you get to the other side in time, right? So here is when your direct
pathway would kind of kick in. So your substantia nigra
would send off these dopamine signals to make
the thalamus more active. And this would make you move a bit more, allow you to go from walking to running to get across the street. But when we lose these dopamine neurons in the substantia nigra,
the substantia nigra can’t send much dopamine to the striatum. So this means that it can’t
amplify the direct pathway. It can’t excite our muscles even more. So we can’t get that extra muscle movement to get our friend here
across the street faster. And on the flip side,
remember that the aim of the indirect pathway,
is to tighten that leash on our thalamus. And that’s to reduce muscle movements. So maybe you made it to the other side, and now you wanna go
from running to walking. So you wanna slow down the muscle activity in your legs, right? So that you can slow down your steps and start to walk. So in this pathway, the
substantia nigra uses its dopamine to kind of, fine-tune
this, and make sure that we don’t turn our muscle
activity down too much, so that you’re, you know, you
wanna walk at a good pace. You don’t wanna walk too slow. So the substantia nigra helps
get you at that perfect pace. And it does this by loosening
our leash on the thalamus. And it causes more movement. When we lose these dopamine
neurons in Parkinson’s disease, the substantia nigra, it
can’t send as much dopamine to the striatum to loosen the
leash on the thalamus, right? So our leash, it gets too
tight, and our muscle movements are turned down too much. So, overall, with a
loss of dopamine neurons in the nigrostriatal pathway,
the substantia nigra, it just can’t initiate more
movement in the direct pathway. And it can’t prevent an
excessive reduction in movement in the indirect pathway,
and that’s why this loss of dopamine neurons in
the substantia nigra causes the slowing down
and loss of movements that we see in someone
with Parkinson’s disease.

About James Carlton

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14 thoughts on “Putting it all together – Pathophysiology of Parkinson’s disease | NCLEX-RN | Khan Academy

  1. What's the difference between Caudate Circuits and the Nigral Stratium pathway? Cuz I thought that Stratium is what stimulates the Substintia Nigra to release Dopamine into the Thalamus…

  2. These videos were great, but a big problem for me is that there is no explanation as to the origin of tremors. If dopaminergic neurons always aim to inhibit the GPI and by doing so increase the activity of the thalamus -> more movement, then why does damaging these neurons cause tremors? In that case there should be a pathway with dopamine that aims to inhibit unwanted movement. You've said that the indirect pathway aims to decrease unwanted movement, but dopaminergic neurons in this pathway still aims to lessen the effects of this pathway, i.e. increase movement. So I'm still not understanding why a loss of dopamin neurons would cause tremors (unwanted movements).

  3. Numbering their videos would be appreciated! This helps to keep track of order in which they are supposed to be watched. Thanks

  4. I love these videos, but the volume is very low. Also….I can only take the Canadian accent for so long…Like nails on a chalkboard.

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