Abstracts

Rationale: Studies indicate that histaminergic system is involved in memory function. On the other hand, patients with pharmacoresistant mesial temporal lobe epilepsy (MTLE) present significant changes in H3 receptors and histamine turnover. However, it is unknown if these alterations are associated with the comorbid cognitive dysfunction that some of these patients suffer. The present study focused to identify an association between cognitive impairment and changes in H3 receptor-induced Gi/o-protein activation and histamine turnover in hippocampus and temporal neocortex of patients with pharmacoresistant MTLE. Methods: NEUROPSI, an abbreviated neuropsychological battery standardized for Spanish and Portuguese speaking people in Latin America, was applied to 19 patients with pharmacoresistant MTLE (31 ± 2.56 years). NEUROPSI comprises specific subtests that allow the evaluation of the following domains: attention and concentration, executive functions, working memory, immediate verbal memory, delayed verbal memory, immediate visual memory, and delayed visual memory. The scores obtained from the different subtests were normalized according to the age and schooling of the patients with MTLE, and then correlated with the tissue content of histamine and tele-methylhistamine (t-MeHA), potency (pEC50) and maximal activation of H3 receptor-induced Gi/o-protein (Emax) estimated in their hippocampus and temporal neocortex. Results: The results obtained from hippocampus revealed the following correlations: the worst performance of motor programming tasks (executive functions) correlated with the lower tissue content of t-MeHA (r = 0.5402, p < 0.05); the poorest performance in digit backward span task (working memory) correlated with the lower ratio t-MeHA/histamine (r = 0.5633, p < 0.05); the worst performance of delayed verbal memory task (long-term memory) correlated with the lower tissue content of histamine (r = 0.5021, p < 0.05). In the temporal neocortex, the highest Emax values correlated with the worst performance of verbal fluency and alternating pattern-stroop tasks (executive functions, r = -0.5805, p < 0.05 and r = -0.5808, p < 0.05, respectively), as well as the overall performance of tasks related with attention and executive functions (r = -0.5869, p < 0.05). No further correlations were detected. Conclusions: It is concluded that the increased H3 receptor-induced Gi/o-protein activation and the lower turnover of histamine in the epileptic hippocampus and temporal neocortex of subjects with MTLE may contribute to their comorbid cognitive deficits. Interventions that lower the H3 receptor activation with the subsequent augmentation in histamine synthesis and release may improve cognitive functions in patients with MTLE. Funding: National Council for Sciences and Technology of Mexico (CONACYT grant 220365 and Scholarship 333114/232762).