Assessment of the expression of 5-HT receptors in thehippocampus of patients with temporal lobe epilepsy with hippocampal sclerosis

[摘要] 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.

[发布机构] University:University of Birmingham;Department:School of Clinical and Experimental Medicine

[关键词] R Medicine;RC Internal medicine