Investigation into the molecular basis of diabetes-induced erectile dysfunction was carried out on corpus cavernosum tissue from control and streptozotocin (STZ)-induced diabetic rats. Increased expression of endothelial nitric oxide synthase (eNOS) and increased nitrosative stress was found in the diabetic penile tissue. Diabetic neuropathy is associated with a failure in axonal regeneration. <i>In vitro</i> axon growth, guidance and regeneration model systems were used to study both the intrinsic nature of diabetic DRG neurones to grow and respond to guidance cues, but also to study the supportive properties of the diabetic nerve environment for axon regeneration. Cyclic Adenosine-3’5-Monophosphate (cAMP) signalling is compromised in diabetic DRG neurones. Increasing cAMP in diabetic neurones reduced the deficit in neurite growth and reversed the aberrant response of diabetic neuronal growth cones to the cAMP-dependent trophic factor, nerve growth factor (NGF). Diabetic neurones display reduced expression of Exchange protein activated by cAMP (Epac), a downstream effector of cAMP. Specifically activating Epac also rescued the abnormal turning responses of diabetic DRG neurones. Impaired axonal regeneration in diabetes has been, in part, attributed to delayed Wallerian degeneration. Using the cryoculture bioassay, it was shown that during regeneration the peripheral nerve environment, of both control and diabetic rats are equally supportive for axon growth. In summary, this is the first study to imply that specific signalling mechanisms, involving the cAMP-Epac pathway, may be compromised in neurones from diabetic rats, which contribute towards reduced neurite growth and abnormal responses to axon guidance cues.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:531909 |
| Date | January 2010 |
| Creators | Steel, Kay Elizabeth |
| Publisher | University of Aberdeen |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Source | http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=158829 |
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