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

被引:10
作者
Banuelos-Cabrera, Ivette [1 ,2 ]
Cuellar-Herrera, Manola [5 ]
Luisa Velasco, Ana [5 ]
Velasco, Francisco [5 ]
Alonso-Vanegas, Mario [6 ]
Carmona, Francia [1 ,2 ]
Guevara, Rosalinda [7 ]
Arias-Montano, Jose-Antonio [3 ,4 ]
Rocha, Luisa [1 ,2 ]
机构
[1] Dept Farmacobiol, Mexico City, DF, Mexico
[2] Ctr Invest & Estudios Avanzados, Dept Pharmacobiol, Mexico City, DF, Mexico
[3] Ctr Res & Adv Studies, Physiol Biophys & Neurosci, Mexico City, DF, Mexico
[4] Ctr Invest & Estudios Avanzados, Mexico City, DF, Mexico
[5] Gen Hosp Mexico, Mexico City, DF, Mexico
[6] Natl Inst Neurol & Neurosurg Manuel Velasco SuCre, Mexico City, DF, Mexico
[7] Univ Nacl Autonoma Mexico, Sch Med, Dept Physiol, Mexico City 04510, DF, Mexico
关键词
Temporal lobe epilepsy; Histamine; Tele-methylhistamine; H-3; receptors; G alpha i/o protein; BRAIN HISTAMINE; RAT; RELEASE; SYSTEM; ANTAGONISTS; GLUTAMATE; SODIUM; DAMAGE;
D O I
10.1111/epi.13329
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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.
引用
收藏
页码:E76 / E80
页数:5
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