Monoamine neurotransmitters in resected hippocampal subparcellations from neocortical and mesial temporal lobe epilepsy patients:: In situ microvoltammetric studies

Abstract

It is known that epilepsy patients diagnosed with neocortical temporal lobe epilepsy (NTLE), differ from those diagnosed with mesial temporal lobe epilepsy (MTLE), e.g., in hippocampal (HPC) pathology. In the present studies, we tested the hypothesis that NTLE and MTLE subtypes of human epilepsy might differ in regards to their HPC monoamine neurochemistry. Monoamine neurotransmitters were studied in separate signals and within s with semiderivative microvoltammetry, used in combination with stearate indicator, Ag–AgCl reference and stainless steel auxiliary microelectrodes. Anterior HPC specimens from the patients’ epileptogenic zone, defined by electrocorticography, were resected neurosurgically from 13 consecutive patients with intractable temporal lobe epilepsy. Four patients were diagnosed with NTLE and nine with MTLE. The criteria for the diagnosis of NTLE versus MTLE was absence versus presence of HPC sclerosis, respectively, based on MRI examination of resected tissue. In addition, NTLE patients demonstrated seizure onset in anterolateral temporal neocortex on electroencephalography (EEG). HPC subparcellations studied were: (a) Granular Cells of the Dentate Gyrus (DG), (b) Polymorphic Layer of DG and (c) Pyramidal Layer: subfields, CA1 and CA2. Dopamine (DA), serotonin (5-HT), norepinephrine (NE) and ascorbic acid (AA) (co-factor in DA to NE synthesis), exhibited separate and characteristic half-wave potentials in millivolts. Each half-wave potential, i.e., the potential at which maximum current was generated, was experimentally established in vitro. Concentrations of neurotransmitters found in HPC subparcellations were interpolated from calibration curves derived in vitro from electrochemical detection of monoamines and AA in saline phosphate buffer. Significant differences between subtypes in concentration of monoamines were analyzed by the Mann Whitney rank sum test and those differences in probability distribution of monoamines were analyzed by the Fisher Exact test; in each case, P<0.01 was the criteria selected for determining statistical significance. DA concentrations were higher in NTLE compared with MTLE in each HPC subparcellation [ P=0.037, 0.024 and 0.007, respectively ( P<0.01)] and DA occurred more frequently in NTLE in the Pyramidal Layer [ P=0.077 ( P<0.01)]. AA was present in one NTLE patient. NE concentrations were higher in MTLE vs. NTLE in each subparcellation [ P=0.012, 0.067 and 0.07, respectively ( P<0.01)] and NE occurred more frequently in MTLE in Granular Cells of DG and Pyramidal Layer [ P=0.052 and 0.014, respectively ( P<0.01)]. In MTLE, NE concentrations in the CA1 subfield of the Pyramidal Layer were decreased vs. the CA2 subfield [ P=0.063 ( P<0.01)]. Serotonin was found in every HPC subparcellation of each subtype but 5-HT concentrations were higher in NTLE vs. MTLE in the Granular Cells of DG and the Pyramidal Layer (CA1 subfield) [ P=0.076 and 0.095, respectively ( P<0.01)]. Thus, this preliminary study showed that marked differences in HPC monoamine neurochemistry occurred in NTLE patients as compared with MTLE patients.