Use this URL to cite or link to this record in EThOS:
Title: Alpha-beta1-42 of LTP is mediated by a signaling pathway involving caspase-3, Akt1 GSK-3beta
Author: Whitcomb, Daniel
ISNI:       0000 0004 2717 5265
Awarding Body: University of Bristol
Current Institution: University of Bristol
Date of Award: 2011
Availability of Full Text:
Access from EThOS:
Amyloid-f31--42 (Af3) is considered a major mediator of the cognitive impairments that are seen in Alzheimer's disease, the leading form of dementia and a growing world-wide health problem. In vitro, Af3 treatment of hippocampal brain slices impairs long-term potentiation and enhances long- term depression, forms of synaptic plasticity, and as such serve to provide cellular correlates of this action. However, the mechanisms underlying these effects are not fully understood. In this thesis the mechanisms underlying the Aj3-mediated dysregulation of synaptic plasticity are therefore explored. Exogenously applied Aj3 was first confirmed to inhibit an NMOAR-dependent form of L TP in the hippocampus (in both acute hippocampal slices and cultured hippocampal slices) and the characteristics of the inhibition of L TP by Aj3 were examined. Next, the inhibition of L TP was found to be reliant on the activation and function of caspases, which themselves have recently been implicated in a newly characterised mechanism of L TO. Finally, evidence is provided showing that this mechanism forms part of a signalling cascade that likely reflects the cleavage and inactivation of Akt-1 by caspases, liberating GSK-3j3 from inhibition - a key L TO-signalling mechanism. These results are best explained by a mechanism whereby the exogenous application of Aj3 causes the induction of L TO signalling. The consequence of which is to inhibit LTP.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available