N122a-neurotrophins - Memory Modulation II Neurotrophic...

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Memory Modulation II: Neurotrophic Factors Mathew Blurton-Jones, Ph.D. N112A, Fall 2011 [email protected]
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Outline What are neurotrophins? What is synaptic plasticity? Do neurotrophins play a role in memory and synaptic plasticity?
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Many post-mitotic neurons die during normal development: Activity-dependant survivial 3
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Rita Levi-Montalcini and Stanley Cohen first discovered that two sarcoma cell lines could promote axonal outgrowth from DRG neurons Rita Levi-Montalcini and Stanley Cohen
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Next they tried to determine if this effect could still occur when you degrade nucelotides, so they treated sarcoma cell extracts with snake venom! Rita Levi-Montalcini and Stanley Cohen
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But the snake venom-treated extracts promoted even more DRG outgrowth!!! Rita Levi-Montalcini and Stanley Cohen
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So could tissue derived from mouse salivary glands Rita Levi-Montalcini and Stanley Cohen
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Identification of nerve growth factor (NGF) as a survival-promoting factor for DRG neurons Rita Levi-Montalcini and Stanley Cohen
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Neuronal survival and growth is regulated by competition for target-supplied trophic factors The yellow cells thrive because they made more connections sooner and outcompete the other cells for neurotrophins
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Cloning of the NGF gene led to the identification of several homologues About 50% amino acid identity in C-terminal biologically active region
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Each neurotrophin preferentially binds a specific Trk (tropomyosin-receptor-kinase) receptor
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SIGMA-ALDRICH Trk receptors mediate the growth promoting effects of Neurotrophins
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The effects of the neurotrophins NGF, BDNF, and NT-3 on the outgrowth of neurites from explanted, dorsal root ganglia (left column), nodose ganglia (middle column), and sympathetic ganglia (right column). From Maisonpierre et al., 1990.) The selectivity of each neurotrophin is mediated by differential Trk expression.
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What is Synaptic Plasticity?
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