Serotonin (5HT) Deficiency but High Tryptophan (L-TP) Concentrations Within Hippocampal Subparcellations in Patients with Mesial Temporal Sclerosis (MTS)
Abstract number :
2.009
Submission category :
Year :
2000
Submission ID :
504
Source :
www.aesnet.org
Presentation date :
12/2/2000 12:00:00 AM
Published date :
Dec 1, 2000, 06:00 AM
Authors :
Patricia A Broderick, Steven V Pacia, Werner K Doyle, Orrin Devinsky, City Univ of New York Medical Sch, New York, NY; NYU Epilepsy Ctr, New York, NY.
Rationale: We have previously demonstrated 5-HT deficiency in the hippocampi (HPC) of patients with MTS. As the first center to enable the detection of L-TP, the precursor to 5-HT, with microvoltammetry, we explored the mechanisms responsible for the 5-HT deficiency by identifying the 5-HT signal and L-TP signal separately, within the same specimen on-line. Methods: We used in situ microvoltammetry with Broderick Probe( stearic acid microelectrodes to detect 5-HT and L-TP in resected HPC subparcellations of 8 patients with mesial temporal lobe epilpesy (MTLE) and 4 with neocortical temporal lobe epilepsy (NTLE). 5-HT and L-TP were detected in separate signals within the same recording (voltammogram) within 1) granular cells of the dentate gyrus (DG) , 2) the polymorphic layer of the DG and 3) HPC pyramidal layer, by characteristic and experimentally derived oxidative potentials, determined in vitro in Ringer's Lactate and PO4Buffer. Ag/AgCl reference and auxillary microelectrodes were placed in each HPC subparcellation 4-6mm from indicator microelectrodes (patented) (manufactured on site). Detailed methods are published ( Broderick, Neurosci. Lett. 95, 1988 and Broderick, Br. Res. 495, 1989). Results: In granular cells of the DG, 5-HT concentrations were significantly lower and L-TP was significantly higher in MTLE patients, in contrast to NTLE patients (Mann Whitney Rank Sum). In the polymorphic layer of the DG and pyramidal layer of the HPC, there was also a trend toward lower 5-HT and higher L-TP concentrations in MTLE patients. Conclusions: Significant 5-HT deficiency along with high L-TP concentrations in the same specimen from granular cells of the DG were found in patients with MTS but not in NTLE patients. This neurochemical profile could result from a malfunction in the L-TP hydroxylase mediated conversion of L-TP to 5-HT or elsewhere in that same pathway. Further study is needed to determine whether excess L-TP is preferentially converted to kynurenine, instead of 5-HT, via the indoleamine 2,3-dioxygenase pathway. Support: Parents Against Childhood Epilepsy (PACE)