Synaptopathy Research Paper

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III.1.3 Aim 1.3. Does CGRP/cAMP potentiate glutamate-induced synaptopathy in organotypic culture? Rationale: As explained in the background, CGRP activates adenylate cyclase increasing the cytosolic cAMP. My preliminary data show that cAMP potentiates increased Ca2+ influx into the SGNs synonymous with the synaptopathy. The preliminary experiments that showed CGRP might potentiate synptopathy was done by Qiong Wang, a former postdoc in our lab. Due to the lack of appropriate antibodies she had to count the axonal fibers instead of synapses. This method is obsolete now, as SGNs are found usually in bundles before they make synapses, which makes this method unreliable. I intend to redo the treatment with CGRP and cAMP in the organotypic culture …show more content…

The mechanism by which cAMP potentiates axon regeneration is largely unclear. In mammals cAMP is considered to act through PKA induced CREB related pathway to promote axon regeneration. cAMP/PKA pathway induces overexpression of synaptotagmin thereby increasing vesicular trafficking to the growth cone surface in a axotomized neuron. Moreover, PKA induced phosphorylation positively regulates synapsin activity inducing neurite growth and SNARE activity. These finding suggest that cAMP/PKA could not only play a part in axon regeneration, but also synapse formation. I intend to study the effect of cpt-cAMP on SGN regeneration and synapse …show more content…

Both NT-3 and BDNF equally promote neurite growth whereas, NT-3 is also involved promoting synapse formation in vitro. I intend to study the SGN regenerative effect of intracochlear perfusion of NT-3 on noise exposed mouse. Similarly, CNTF is found in the organ of corti and it was found that CNTF expression goes down in deafened rats at about the same time as SGNs start to die. It was show in retinal ganglion cells that CNTF can promote regeneration. This shows that apart from neuronal survival CNTF could also promote

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