Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.663312
Title: AMPA receptor potentiators : mechanisms of neuroplasticity
Author: Voss, Oliver Paul
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2007
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Abstract:
The AMPA receptor potentiator LY404187 is able to significantly increase the average length of neuritic processes in the neuroblastoma cell line SH-SY5Y only in the presence of s-AMPA, and this response is dependent on AMPA receptor activation. The compound also increases neurofilament protein levels as well as levels of the BDNF receptor Trk-B. The increase in neuritic length is blocked by addition of an antibody specific for BDNF indicating that this neurotrophin is required for the induction of neurite growth. The ability to induce morphological change in neuronal processes of the compound was then tested in a rodent model of lesions and sprouting. Unilateral ibotenic lesions of the entorhinal cortex in mice produce a progressive and substantial loss of synapses in the molecular layer of the dentate gyrus. Twice daily s.c. injections of LY404187 for 14 and 28 days post-lesion did not produce any significant change in synaptophysin immunoreactivity in the dentate gyrus. There was also no change in the volume of the lesion in the entorhinal cortex. In a secondary study the rate of neurogenesis in the dentate gyrus was also measured. Administration of LY404187 failed to induce a change in the number of BrdU +ve cells within the sub-granular zone of the dentate gyrus. Any long term structural of behavioural change caused by prolonged AMPA receptor potentiation is likely to be underpinned by changes in protein expression. The levels of key proteins involved in the intracellular response to AMPA receptor activation were measured by Western Blot and immunohistochemistry and levels of the neurotransmitters dopamine and serotonin were measured by HPLC. The effect of chronic administration to the AMPA receptor potentiator LY450108 on the rate of neurogenesis and the development of newly born neuron in the hippocampus was also investigated.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.663312  DOI: Not available
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