Departamento de Farmacobiología, Centro de Investigación y de Estudios Avanzados, México.
Neurobiol Dis. 2012 Jan;45(1):499-507. doi: 10.1016/j.nbd.2011.09.006. Epub 2011 Sep 21.
Experiments were designed to evaluate different variables of the dopaminergic system in the temporal cortex of surgically treated patients with temporal lobe epilepsy (TLE) associated with mesial sclerosis (MTLE, n=12) or with cerebral tumor or lesion (n=8). In addition, we sought to identify dopaminergic abnormalities in those patients with epilepsy that had comorbid anxiety and depression. Specifically, we investigated changes in dopamine and its metabolites, D1 and D2 receptors, tyrosine hydroxylase (TH) and dopamine transporter. Results obtained from patients with epilepsy were compared with those found in experiments using autopsy material. The neocortex of patients with MTLE demonstrated high D1 expression (1680%, p<0.05) and binding (layers I-II, 31%, p<0.05; layers V-VI, 28%, p<0.05), and decreased D2 expression (77%, p<0.05). The neocortex of patients with TLE secondary to cerebral tumor or lesion showed high expression of D1 receptors (1100%, p<0.05), and D2-like induced activation of G proteins (layers I-II, 503%; layers III-IV, 557%; layers V-VI, 964%, p<0.05). Both epileptic groups presented elevated binding to the dopamine transporter and low tissue content of dopamine and its metabolites. Analysis revealed the following correlations: a) D1 receptor binding correlated negatively with seizure onset age and seizure frequency, and positively with duration of epilepsy; b) D2 receptor binding correlated positively with age of seizure onset and negatively with duration of epilepsy; c) dopamine transporter binding correlated positively with duration of epilepsy and frequency of seizures; d) D2-like induced activation of G proteins correlated positively with the age of patients. When compared with autopsies and patients with anxiety and depression, patients without neuropsychiatric disorders showed high D2-like induced activation of G proteins, an effect that correlated positively with age of patient and seizure onset age, and negatively with duration of epilepsy. The present study suggests that alterations of the dopaminergic system result from epileptic activity and could be involved in the physiopathology of TLE and the comorbid anxiety and depression.
实验旨在评估手术治疗的颞叶癫痫（TLE）伴内侧硬化（MTLE，n=12）或伴脑肿瘤或病变（n=8）患者颞叶皮质中不同的多巴胺能系统变量。此外，我们试图确定那些患有癫痫伴发焦虑和抑郁的患者中存在多巴胺能异常。具体而言，我们研究了多巴胺及其代谢物、D1 和 D2 受体、酪氨酸羟化酶（TH）和多巴胺转运体的变化。将从癫痫患者中获得的结果与使用尸检材料进行的实验结果进行比较。MTLE 患者的新皮质显示 D1 表达增加（1680%，p<0.05）和结合（I-II 层，31%，p<0.05；V-VI 层，28%，p<0.05），以及 D2 表达减少（77%，p<0.05）。脑肿瘤或病变继发 TLE 患者的新皮质显示 D1 受体高表达（1100%，p<0.05），D2 样诱导的 G 蛋白激活（I-II 层，503%；III-IV 层，557%；V-VI 层，964%，p<0.05）。两个癫痫组均表现出多巴胺转运体结合增加和多巴胺及其代谢物组织含量降低。分析显示出以下相关性：a）D1 受体结合与癫痫发作年龄和发作频率呈负相关，与癫痫持续时间呈正相关；b）D2 受体结合与癫痫发作年龄呈正相关，与癫痫持续时间呈负相关；c）多巴胺转运体结合与癫痫持续时间和发作频率呈正相关；d）D2 样诱导的 G 蛋白激活与患者年龄呈正相关。与尸检和焦虑及抑郁患者相比，无神经精神障碍的患者表现出高 D2 样诱导的 G 蛋白激活，这种效应与患者年龄和癫痫发作年龄呈正相关，与癫痫持续时间呈负相关。本研究表明，多巴胺能系统的改变是由癫痫活动引起的，可能与 TLE 的病理生理学以及伴发的焦虑和抑郁有关。
