Bioimaging L-Tryptophan in Human Hippocampus and Neocortex

Abstract

We have previously demonstrated serotonin (5-HT) alterations in the hippocampi (HPC) and neocortices of patients with mesial temporal lobe epilepsy (MTLE) as compared with those presenting with neocortical temporal lobe epilepsy (NTLE). Now, we extend these findings by analysis of L-tryptophan (L-Trp) concentrations, recorded within the same patient population. We used an electrochemical technology, that is, neuromolecular imaging (NMI) with a novel miniature sensor, the carbon-based BRODERICK PROBE®. These sensors detected L-Trp in resected HPC subparcellations as well as in temporal lobe neocortex of patients diagnosed with either MTLE or NTLE. Five patients were classified as NTLE and nine as MTLE based on magnetic resonance imaging (MRI) and intracranial EEG evaluations. HPC subparcellations studied in 12 of 14 patients were (1) granular cells of the dentate gyrus (DG); (2) polymorphic layer of the DG; and (3) HPC pyramidal layer. Layer IV of temporal neocortex was studied in all 14 patients. A specific oxidation potential voltametrically provided the signature for L-Trp. The results showed that in granular cells of DG and, in pyramidal layer, L-Trp concentrations were significantly higher in MTLE patients in contrast to NTLE patients (p < 0.05, Mann-Whitney rank sum). Taken together with our recently published data, L-Trp concentrations were inversely proportional to 5-HT concentrations in these neuroanatomic substrates. In polymorphic layer of the DG, there was a trend toward lower 5-HT and higher L-Trp concentrations in MTLE patients. In neocortical layer IV, NTLE patients had significantly lower L-Trp concentrations than MTLE patients; however, 5-HT concentrations were similar in both groups (p < 0.01, Mann-Whitney rank sum). Our results indicate markedly different alterations in L-Trp and 5-HT synthesis and metabolism in the epileptogenic temporal lobes of patients with MTLE as compared with NTLE. Considering that various L-Trp metabolites may have proconvulsant or anticonvulsant properties, these alterations have important implications in the pathogenesis of both types of epilepsy.