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PNS II: Neurotrophin 2.28.

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Neurotrophin hypothesis: a population of neurons that compete for a specific growth factor, so
some of the neurons that don’t get to the target in time will die. TrkB is selective for BDNF and
NT4. TrkC is selective for neutrophin-3. TrkA is selective for NGF. P75 on its own or partnering
with another receptor can actually cause cell death, so it’s interesting that these neurotrophins
that promote cell proliferation can attach to p75 and cause cell death. It’s also possible that the
pro forms of these neurotrophins can be released, and they will not bind to the Trk proteins.
Pro BDNF does not bind to TrkB but can bind to p75 to cause cell death as well as growth cone
collapse as well as dendritic spine collapse. Sympathetic neurons are NGF dependent and
express TrkA and p75. Peripheral neurons also depend on neurotrophins; nociceptors are NGF
sensitive, so getting rid of NGF will eliminate pain response.

All dorsal root ganglia are glutamatergic, and release glutamate into the spinal cord and
activate two kinds of interneurons. One will be inhibitory to the effector muscle so that it
doesn’t activate that motor neuron. The other will activate the motor neuron on the muscle on
the other side, causing an opposite reaction (think leg hammer reflex).

Extrinsic and intrinsic apoptotic pathways. An outside ligand that activates the caspase
pathway: 8 cleaves 3 (the ultimate caspase with a ton of substrates, including a substrate that
releases a DNase to cut DNA). 8 cleaves Bid (Bcl-2 protein family), which becomes pro-death
and activate Bax to form a pore in the mitochondrion, letting out cytochrome C. This forms the
apoptosome to also activate caspase-3 to cause cell death. Intrinsic pathway: DNA damage
causes p53 to activate some of the Bcl-2 proteins to activate caspase-3 and induce cell death.

BENF is required for long-term memory in an inhibitory avoidance paradigm. If mice are
trained, BDNF levels increase. So where does BDNF function? It appears to function both pre
and post synaptically.

Counting the number of dendritic spines, you would have the number of synapses with axons.
Adding BDNF to these systems, you find more dendritic spines, suggesting that BDNF is
affecting the postsynaptic side.

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