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Dissertation
Role of somatostatin receptor subtypes in antiepileptic actions of somatostatin
Doctor of Philosophy (Ph.D.), Drexel University
May 2007
DOI:
https://doi.org/10.17918/00009983
Abstract
Somatostatin (SST) is an inhibitory neuropeptides extensively distributed in the brain and peripheral tissues. It has been shown to have robust antiepileptic actions in rat. However, the cellular mechanisms for its antiepileptic effect are unclear. This thesis work aims to determine which SST receptor subtype(s) mediates its antiepileptic effect and to explore the cellular mechanisms pertinent to its antiepileptic actions. Behavioral animal models and eletrophysiological techniques are used to achieve the goal. We show here that SST2, SST3 and SST4 receptor subtypes are all involved in seizure control after systemic injection of PTZ and kainic acid, although SST4 plays the most prominent role. We also show that SST 2 and SST4 are the major receptors in mediating the inhibitory effect of SST on epileptiform spontaneous bursting in the CA1 region of mouse hippocampus. Further, SST enhances M-currents (IM) in CA1 pyramidal neurons of mouse hippocampus, although it does not affect leak currents (IK(L)) and excitatory postsynaptic currents (EPSCs), as has been reported for this peptide in rat. SST4 is the receptor through which SST increases IM. In addition, blockade of M-channels significantly reduces the inhibitory effect of SST in the epileptiform spontaneous bursting in the CA1 region. Therefore, these results show that SST and its receptors are important in controlling seizure activity in mice, and in the CA1 region, SST4-mediated increase in M-currents apparently plays an important role in SST antiepileptic effects.
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Details
- Title
- Role of somatostatin receptor subtypes in antiepileptic actions of somatostatin
- Creators
- Cuie Qiu
- Contributors
- Melanie Tallent (Advisor) - Drexel University, Drexel University (1970-)
- Awarding Institution
- Drexel University
- Degree Awarded
- Doctor of Philosophy (Ph.D.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- ix, 145 pages
- Resource Type
- Dissertation
- Language
- English
- Academic Unit
- College of Medicine; Pharmacology and Physiology; Drexel University
- Other Identifier
- 991021888955004721