BIO SCI 44 Lecture Notes - Lecture 11: Substantia Nigra, Diabetes Mellitus Type 1, Synaptic Plasticity

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9 Feb 2017

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Cell Replacement Strategies
I. Can our brain regenerate?
A. Adult neurogenesis
B. Adult plasticity
C. Both of these are limited in their capacity to regenerate
II. What are some ways stem cells might be used to treat brain diseases?
A. Cell replacement
B. Promoting plasticity
C. Delivery of therapeutic proteins
D. Disease modeling and drug discovery
III. Examples of Cell Replacement Strategies
A. Type 1 Diabetes: loss of beta cells in pancreas that produce insulin
1. Stem cells used o make new beta cells and then transplant them. . ?
B. Heart Attack: cardiomyocytes die from lack of oxygen
1. Fix vascular supply. . . ?
IV. Cell replacement strategies in Brain
A. Neurons are connected
B. Parkinson’s Disease
1. Tremor, rigidity, slow movement, freezing, shuffling steps (Motor
2. Caused by degeneration of dopamine producing neurons in substantia
a) In substantia nigra, the process starts here and then move towards
other places
C. Reduced level of neurotransmitter dopamine causes many of the symptoms of PD
(this can be seen by PET scan)
1. Why is there a lost → because they lost cells that make dopamine
V. Solution- replace dopaminergic neurons
A. Make dopaminergic neurons or precursors from stem cells
B. Transplants cells that can survive and mature into dopaminergic neurons (done by
neurosurgery and not injection because it will not do anything)
C. Have neurons grown axons to the target (striatum)
D. Form appropriate synaptic connections within target
E. The last two steps are more challenging because of the issue of connectivity
VI. How can we make sure there is a right connectivity (axonal growth)?
A. Provide a source of neurotrophins in target regions (combine stem cells with
growth factors)
1. Growth factor = neurotrophins
a) Neurotrophins can be trophic (survival promoting) or tropic
(directing axonal outgrowth)
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