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Current time:0:00Total duration:7:46

Biological basis of parkinson's disease

Video transcript

in this video I'm going to talk about the biological basis of Parkinson's disease Parkinson's disease Parkinson's disease is a progressive neurological disorder involving motor abnormalities and often mental dysfunction as well many motor abnormalities may occur but the most common are slowed movements a type of tremor a type of increased muscle tone a type of abnormal walking and poor balance leading to Falls so in this drawing of a person with Parkinson's disease this is a very typical way the person with advanced Parkinson's disease will walk where they're slow they're kind of stooped and shuffling and often the hands have a tremor to them and if you ask them to relax and you try to move their muscles around their muscles are stiffer than normal they feel slow and stiff and then they often have the tremor as well late in the course of the disease when motor abnormalities are severe patients may become unable to care for themselves and may also develop abnormalities of cognitive emotional or autonomic functions the brains of patients with Parkinson's disease often have an abnormality that is visible to the naked eye here if we look at this normal brain that's been cut from the top to the bottom so this is the right half and this is the left half and if we look not at the cerebrum this part on the top but this part on the bottom called the brain stem there's a small part of the brain stem right here and right here called the substantia [ __ ] let me just write that term out sub stanchion [ __ ] and this term substantia [ __ ] just means black substance because these areas are darker than the surrounding brain tissue with Parkinson's disease the substantia [ __ ] is less dark or it's not dark at all sometimes you can't see any dark spots here like we do in a normal brain and if we look with a microscope we can see that inside the substantia [ __ ] there's been the loss of a particular kind of neuron that's pigmented giving at the dark color the rest of the cells and the tissue in this area look pretty normal suggesting the with Parkinson's disease it's only a specific type of neuron that's lost while sparing the rest of the brain tissue at least early in the course of the disease these cells are dopaminergic neurons meaning they are neurons that release the neurotransmitter dopamine at synapses with other neurons let me just write dopamine an important neurotransmitter that lets neurons communicate with each other there are other small collections of dopaminergic neurons scattered around the central nervous system and it turns out these cells may also be lost with Parkinson's disease but it appears that most of the motor abnormalities the movement problems that occur are from the change that happens to the substantia [ __ ] where these dopaminergic neurons are lost this illustration is showing that same thing but here we're looking up at the brain from underneath and they've cut off the brainstem at the level of the substantia [ __ ] and they're showing that in a person without Parkinson's disease we usually see this dark area very well the substantia [ __ ] on both sides but in a person with Parkinson's disease since those pigmented dopaminergic neurons have been lost we often see less or none of that darkness that we normally see in the substantia [ __ ] the substantia [ __ ] is one part of a collection of structures called the basal ganglia let me write that term out basal ganglia so here on this illustration they're showing that if we take the brain and section it from top to bottom and then we look deep inside the cerebrum all these areas that they've colored here represent this collection of structures called the basal ganglia and one part of that is the substantia [ __ ] and here's the same thing kind of zoomed in and here down here is the substantia [ __ ] in this illustration the basal ganglia plays a major role in motor functions as well as some mental functions the wiring of the basal ganglia is complex and incompletely understood as you can tell by how busy and complicated this diagram looks with lots of pluses and minuses because certain areas excite other areas in certain areas inhibit other areas but the simplistic way I think about the basal ganglia is that it receives information from many places in the nervous system and importantly from the outermost layer of the cerebrum the cerebral cortex the basal ganglia then performs complex processing of that information in a way we don't totally understand yet and then the basal ganglia sends information back to areas of the cerebral cortex influencing its activity such as the motor cortex for motor tasks the primary output of the substantia [ __ ] is to another part of the basal ganglia called the striatum and the loss of these dopamine neurons projecting from the substantia [ __ ] to the striatum appears to cause most of the motor abnormalities of Parkinson's disease when we look under the microscope we can see diseased neurons that are degenerating in the substantia [ __ ] like this neuron right here and they often contain abnormal structures like this which are called Lewy bodies so let me just write that out Lewy body these abnormal structures we can see inside the degenerating dopaminergic neurons of the substantia [ __ ] in Parkinson's disease these Lewy bodies primarily contain a protein called alpha synuclein let me write that out too alpha sinn nucleon this alpha-synuclein is a normal protein that's present in brain cells under normal conditions but for unclear reasons in Parkinson's disease it appears that the alpha synuclein is not cleared normally from the neurons and then it clumps together inside the neurons to form Lewy bodies so how the Lewy bodies form is not entirely clear and another thing that's not clear is if the Lewy bodies form and that kills the dopaminergic neurons in the substantia [ __ ] or if something else is killing the dopaminergic neurons and these Lewy bodies are just formed as a byproduct of that process with severe Parkinson's disease that also includes cognitive dysfunction there is often widespread Lewy body deposition and neuronal loss not just in the substantia [ __ ] but throughout the cerebral cortex this outermost layer of the cerebrum and there's also a separate condition that's related but separate called Lewy body disease where there's less motor abnormalities from basal ganglia dysfunction and more cognitive dysfunction from loss of neurons throughout the cerebral cortex a few things have been associated with the risk of developing Parkinson's disease several genetic mutations have been found in some families that have an inherited form of the disease and some other studies have suggested that rural living possibly with exposure to agricultural chemicals may be a risk factor although it's unclear how these factors might cause or contribute to the disorder because most of the symptoms are caused by loss of a small population of a similar kind of neuron in the substantia [ __ ] Parkinson's disease is a leading candidate for the possibility of treatment with stem cells and intense research is ongoing to see if these cells can be replaced safely and effectively