Pharmacoresistant temporal lobe epilepsy modifies histamine turnover and H3 receptor function in the human hippocampus and temporal neocortex

Experiments were designed to evaluate the tissue content of tele-methylhistamine (t-MeHA) and histamine as well as H-3 receptor (H(3)Rs) binding and activation of the heterotrimeric guanine nucleotide binding alpha i/o proteins (G alpha i/o) coupled to these receptors in the hippocampus and temporal neocortex of patients (n = 10) with pharmacoresistant mesial temporal lobe epilepsy (MTLE). Patients with MTLE showed elevated tissue content of t-MeHA in the hippocampus. Analyses revealed that a younger age at seizure onset was correlated with a higher tissue content of t-MeHA, lower H3R binding, and lower efficacy of G alpha i/o protein activation in the hippocampus. We conclude that the hippocampus shows a reduction in the H3R function associated with enhanced histamine. In contrast, the temporal neocortex displayed a high efficacy of H(3)Rs G alpha i/o protein activation that was associated with low tissue contents of histamine and t-MeHA. These results indicate an overactivation of H(3)Rs leading to decreased histamine in the temporal neocortex. However, this situation was lessened in circumstances such as a longer duration of epilepsy or higher seizure frequency. It is concluded that decrease in H(3)Rs function and enhanced levels of histamine may contribute to the epileptic activity in the hippocampus and temporal neocortex of patients with pharmacoresistant MTLE.