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Download StatisticsAlomar, Hatun (2017). Assessment of the expression of 5-HT receptors in the hippocampus of patients with temporal lobe epilepsy with hippocampal sclerosis. University of Birmingham. Ph.D.
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Alomar17PhD.pdf
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Abstract
Temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) is the most common type of pharmaco-resistant epilepsy. It is characterised by recurrent focal onset seizure that affects the medial part of the temporal lobe, in particular, the hippocampus. Patients with TLE-HS suffer from typical aura symptoms, especially epigastric aura, in addition to psychological symptoms which include dysmnestic symptoms such as memory impairment and fear. As a result of the important role of the serotonergic system in human brain physiological and pathological functions and the crucial need to identify a novel target to control seizure among this type of patient, some serotonergic excitatory (5-HT\(_2\)\(_A\), 5-HT\(_3\)A, 5-HT\(_4\) and 5-HT\(_7\)) and inhibitory (5-HT\(_1\)\(_A\)) receptors were selected to study using immunohistochemistry in the human TLE-HS hippocampus, in addition to the purinergic receptors (P2x\(_7\)) and the orphan G-protein (GPR61). The results indicate variable degree of upregulation of 5-HT\(_3\)A, 5-HT\(_1\)\(_A\), 5-HT\(_4\), GPR61 and P2x\(_7\) receptors in the sclerotic hippocampi of TLE-HS patients. Subsequent studies focused on the 5-HT\(_3\)A receptors expression; the overexpression of this excitatory receptor was established using immunohistochemistry, SDS-PAGE western blot, receptor autoradiography and radioligand binding assays that give comparable results. The upregulation of the excitatory 5-HT\(_3\)A receptor in the excitatory neurons of hippocampus may contribute to the neuronal hyperexcitability evident among TLE-HS patients. This study proposed 5-HT\(_3\) receptors as a novel target to antagonise to control seizure in TLE-HS patients and improve their quality of life.
| Type of Work: | Thesis (Doctorates > Ph.D.) | |||||||||
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| Award Type: | Doctorates > Ph.D. | |||||||||
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| College/Faculty: | Colleges (2008 onwards) > College of Medical & Dental Sciences | |||||||||
| School or Department: | School of Clinical and Experimental Medicine | |||||||||
| Funders: | None/not applicable | |||||||||
| Subjects: | R Medicine > RC Internal medicine | |||||||||
| URI: | http://etheses.bham.ac.uk/id/eprint/7143 |
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