Monoamines and their metabolites in cerebrospinal fluid and temporal cortex of epileptic patients

Hippocampal serotonin depletion is related to the presence of generalized tonic–clonic seizures, but not to psychiatric disorders in patients with temporal lobe epilepsy

“…Studies using HPLC in human tissue have shown that 5HT and 5-hydroxyindoleacetic acid levels are increased (Louw et al, 1989;Naffah-Mazzacoratti et al, 1996;Pintor et al, 1990) or unaltered (Mori et al, 1987) in the spiking compared to non-spiking temporal cortices of patients with complex partial seizures. However, these previous studies evaluating serotonin concentrations in humans are not suitable for comparison with ours because the correlations of the serotonin levels with clinical variables were not examined or the study designs and sample sizes were quite different.…”

“…Although TLE-HS represents an excellent model for the study of the role of [5HT]s in humans, scarce data from human brain tissue, particularly the hippocampal tissue of patients with epilepsy, are available (Broderick et al, 2000;Louw et al, 1989;Mori et al, 1987;Naffah-Mazzacoratti et al, 1996;Pacia et al, 2001;Pintor et al, 1990).…”

Protective activity of α-lactoalbumin (ALAC), a whey protein rich in tryptophan, in rodent models of epileptogenesis

“…Agents that increase extracellular 5-HT levels, such as 5-hydroxytryptophan (5-HTP) and/or SSRIs, inhibit generalized tonic-clonic seizures as well as focal seizures, including hippocampal and lateral geniculate nucleus-kindled seizures and spontaneous seizures occurring after pilocarpine-induced SE, whereas, they increase absence seizures (for a review see Bagdy et al, 2007). In humans, a link between altered 5-HT, seizures and epilepsy is suggested by the finding of reduced levels of 5-HT metabolites in the cerebrospinal fluid of patients with seizure disorders (De Grandis et al, 2010), reduced in vivo 5-HT binding, mostly to 5-HT 1A receptors, in patients with chronic epilepsy (Merlet et al, 2004) and a possibly compensatory increase in 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) content in cortex tissue resected from patients with pharmacoresistant epilepsy (Naffah-Mazzacoratti et al, 1996). Based on these findings, the suggestion has been made that modulation of serotoninergic function could represent an innovative approach to the treatment of AED-refractory epilepsy (Lo¨scher and Leppik, 2002).…”

Cerebrospinal Fluid Levels of Monoamine Metabolites in the Epileptic Baboon

“…The precision of this methodology is high and was validated with specific gas chromatographic-mass spectrometric (GS-MS) assays for each metabolite [20]. Overall, monoamine metabolite levels are relatively stable and more reliable than monoamine levels in the CSF [5] because monoamines are rapidly metabolized in brain tissue [6]. …”

“…Of the three, 5-HT and DA have the most consistent effects on seizure threshold. Their metabolites are increased both in epileptogenic tissue as well as in the cerebrospinal fluid in people with chronic epilepsy undergoing resective surgery [5]. In rodent hippocampi, 5-HT release was briefly increased immediately after onset of pilocarpine-induced status epilepticus, whereas its main metabolite, 5-hydroxyindolacetic acid (5-HIAA) increased only two days later, indicating that the 5-HT was being metabolized locally [6].…”