Sensitises pain pathways. It's upregulated in inflammation
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Where is BDNF synthesised
in primary sensory neurons and transported to their central terminals
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How does it alter pain processing?
through altered gene expression, NMDA receptor activation and trafficking.
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What kind of receptor does BDNF signal through
TrkB receptors.
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What happens when the BDNF binds
the two inactive monomers dimerize and phosphorylate
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What couples to active BDNF receptors
GRB2 (GPCR binding protein 2) and Sos (Son of sevenless, a guanine nucleotide exchange factor)
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What does the trk-B/GRB2/SOS complex do?
Activates Ras, a small GTPase which becomes active when bound to GTP
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What does Ras do?
Activates a MAP kinase cascade. resulting in active MAP kinase, which translocates to the nucleus to activate transcription factor
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How is the signal amplified?
Increasing the number of active signalling molecules at each stage in a cascade.
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What is one effect of local [cAMP]
Influence on memory formation, via pKA and CREB phosphorylation.
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How many isoforms of adenyl cyclase are there in the CNS
Eight
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What is common to all of them
they are all activated by Gas, all inhibited by Gai, and they all have TM domains bound to the membrane
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What is different about I, III and VIII
they are activated by calcium, calmodulin.
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What is different about V and VI
Inhibited by calcium
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What mediates the effect of cAMP
cAMP dependant PKA, which can phosphorylate ion channels, enzymes, transcription factors
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What's an AKAP
An A-kinase anchoring protein.
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What do AKAPs do?
use scaffold proteisn to restrict secondary messenger production to subcellular regions to maintain specificty of effects. Bind other signalling molecules to inegrate different signal pathways.
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Another way that spatio-temporal localisation is maintained
The physical properties of second messengers restrict signalling to specific regions, eg DAG in the membrane
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