4 - 5 - 36. Parkinson's disease. Pathophysiology; non-human models (16-37)

4 - 5 - 36. Parkinson's disease. Pathophysiology; non-human models (16-37)

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Hello in, Hello. In this lecture we're going to talk about Parkinson's Disease specifically pathophysiology in non-human models for the disease. First of all we have to say explicitly that most cases of Parkinson's Disease have an unexplained cause. In general. People suspect that dopaminergic neurons may be selectively vulnerable because the cell body of the dopaminergic neuron must maintain large amounts of axoplasm and presynaptic proteins. Here is the cell body and as you know it projects to many areas of the central nervous system. Many parts of the brain. And so it is maintaining an enormous amount of. Citosol in its axon and at its axon terminals, and this puts a tremendous burden on the cell body, which must then be maintained for many decades of life. Specifically, dopaminergic neurons may also be selectively vulnerable. Now, of course there are many types of neurons. That have large axons. And, in fact, there are neurode-, degenerative diseases that correspond to. Most of them, the motor neuron in the spinal cord. is susceptible to Amyotrophic Lateral Sclerosis which we will not have a chance to discuss in this course. The large Purkinje cell of the cerebellum degenerates in some ataxias. And as we've mentioned the large cholinergic neurons of the basal forebrain can degenerate in Alzheimer's Disease. Why each of these is selectively vulnerable in a certain disease. Is not understood. Dopaminergic neurons may be selectively vulnerable in some cases because dopamine is highly reactive. here are these two adjacent hydroxyl groups, a catechol group, and they are selectively. Excensor accessible to oxidizing agents, and they then form reactive oxygen species themselves. And so, over a period of decades and decades, one has a build up of reactive oxygen species inside neurons. Another cause of Parkinson's disease seems to be pesticides. There's a very nice paper by my friends at UCLA on pesticides in the central valley of California. In people who are selectively exposed to those pesticides. Who have a high er incidence of Parkinson's disease. And then there is the frozen attic episode several decades ago. in the San Francisco Bay area, there was an impurity in synthetic heroin. which was taken up by the dopamine transporter. As you'll remember, the dopamine transporter is expressed only in dopaminergic cells. This impurity was changed to another. Compound, and it killed dopaminergic neurons quite drastically. Even before then, the
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influenza pandemic, worldwide epidemic of 1918, killed 20,000,000 people. In many people, the flu specifically killed dopaminergic neurons. Some of the survivors of that epidemic lived through the 60's and they were studied when Oliver Sacks was a young doctor. in The Bronx, I believe, and that was the story of his book called "Awakenings" and of the film based on that story. he has gone on to write many wonderful books at the intersection of neuroscience and medicine.
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