Abstracts

Rationale: Studies indicate that H3 receptors modulate the histamine neuron activity. The present study was focused to clarify whether human mesial temporal lobe epilepsy (MTLE) is associated with changes in H3 receptors and histamine turnover.Methods: Experiments were designed to determine the histamine turnover (tissue content of tele-methylhistamine (t-MeHA) and histamine) as well as H3 receptor binding and activation of Gi/o proteins in the epileptic hippocampus and temporal neocortex of surgically treated patients (n=10) with pharmacoresitant MTLE. Results obtained from autopsies (n=6) were used as control situation.Results: The averages of the different paramenters evaluated from hippocampus of patients with MTLE did not demonstrate significant differences when compared with the averages of the autopsy group. However, correlation analysis of the results obtained from hippocampus with the clinical data of the patients revealed that the older the age of seizure onset, the higher the binding to H3 receptors (r=0.7719, p<0.05), and the higher H3 receptors-induced maximal stimulation of Gi/o proteins (r=0.7694, p<0.05). The temporal neocortex of patients with MTLE demonstrated low t-MeHA/histamine ratio (p<0.05). It also showed high H3 receptors-induced maximal stimulation of Gi/o proteins (130.5%, p<0.001), an effect that correlated with the shorter duration of epilepsy (r=-0.7707, p<0.05). No further changes were detected.Conclusions: The present study indicates an overactivation of the H3 receptors associated with a decrease in the histamine neuron activity in brain areas involved in the human MTLE. Our results also indicate that this situation is more evident at the early stages of the illness. Supported by CONACyT scholarship 333114/232762