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Putting it all together - Pathophysiology of Parkinson's disease

Video transcript

so we know that Parkinson's disease causes problems with movements right and and what we see in people with Parkinson's disease is a reduction a loss of slowing down of movements and 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 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 [ __ ] and you might remember this that the substantia [ __ ] 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 [ __ ] so they they head over they project to the striatum so let's let's draw some of these so here's some dopamine neurons here in the substantia [ __ ] and they go over here to the striatum so they send their axons 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 [ __ ] to the striatum and we call it the Nigro striatal pathway [ __ ] because they head from the substantia [ __ ] 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 and actually this is really interesting so so as these neurons are starting to die as we're starting to lose these 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 and we're not going to go into the the kind of the pathological diagnosis of Parkinson's disease at this point but in 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 that we we actually don't know at this point what role Lewy bodies play in the disease we don't know if there may be 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 an interesting bit of research that's currently going on so anyway so 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 percent of them so quite a bit right 80 percent that's when we start to see brady kinesia 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 is 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 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 want to 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 [ __ ] would send off these dopamine signals to make the thalamus more active and 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 [ __ ] the substantia [ __ ] can't and 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 want to go from running to walking so you want to 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 [ __ ] 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 want to walk at a good pace you don't want to walk too slow so the substantia [ __ ] 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 [ __ ] 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 the nigrostriatal pathway the substantia [ __ ] 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 [ __ ] causes the slowing down and loss of movements that we see in someone with Parkinson's disease