Monocarboxylate transporter 1 is deficient on microvessels in the human epileptogenic hippocampus.
Monocarboxylate transporter 1 is deficient on microvessels in the human epileptogenic hippocampus.
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DOI：
10.1016/j.nbd.2010.11.005
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发表时间：
2011-02
影响因子：
6.1
通讯作者：
Eid, Tore
中科院分区：
文献类型：
--
作者：
Lauritzen, Fredrik;de Lanerolle, Nihal C.;Lee, Tih-Shih W.;Spencer, Dennis D.;Kim, Jung H.;Bergersen, Linda H.;Eid, Tore
关键词：
单羧酸转运体1(MCT1)促进重要的代谢燃料(乳酸、丙酮酸和酮体)的运输，也可能促进丙戊酸等酸性药物通过血脑屏障的运输。由于大脑能量代谢受损和抗癫痫药物抵抗是颞叶癫痫(TLE)的共同特征，我们试图研究MCT1在该疾病患者脑组织中的表达。应用免疫组织化学和免疫金电镜法检测TLE合并海马区硬化症(简称内侧TLE或MTLE，n=15)、TLE伴非海马区硬化症(Non-MTLE，n=13)和神经学正常尸检者(n=8)脑组织中MCT1的分布。在尸检对照组和非MTLE组中，MCT1存在于贯穿整个海马区的广泛的微血管网络中，程度较轻。与非MTLE患者相比，MTLE患者海马区多个部位微血管上MCT1的表达明显缺失，尤其是CA1，内皮细胞膜上MCT1的表达缺失37%~48%。这些发现表明，血液来源的单羧酸盐燃料的摄取，可能还有酸性药物，如丙戊酸，在致痫的海马体中受到干扰，特别是在MTLE中。我们假设MCT1在脑微血管上的缺失与耐药TLE的病理生理机制有关，并提出MCT1的重新表达可能是治疗该疾病的一种新途径。
Monocarboxylate transporter 1 (MCT1) facilitates the transport of important metabolic fuels (lactate, pyruvate and ketone bodies) and possibly also acidic drugs such as valproic acid across the blood brain barrier. Because an impaired brain energy metabolism and resistance to antiepileptic drugs are common features of temporal lobe epilepsy (TLE), we sought to study the expression of MCT1 in the brain of patients with this disease. Immunohistochemistry and immunogold electron microscopy were used to assess the distribution of MCT1 in brain specimens from patients with TLE and concomitant hippocampal sclerosis (referred to as mesial TLE or MTLE (n = 15)), patients with TLE and no hippocampal sclerosis (non-MTLE, n = 13) and neurologically normal autopsy subjects (n = 8). MCT1 was present on an extensive network of microvessels throughout the hippocampal formation in autopsy controls and to a lesser degree in non-MTLE. Patients with MTLE were markedly deficient in MCT1 on microvessels in several areas of the hippocampal formation, especially CA1, which exhibited a 37 to 48% loss of MCT1 on the plasma membrane of endothelial cells when compared with non-MTLE. These findings suggest that the uptake of blood-derived monocarboxylate fuels and possibly also acidic drugs, such as valproic acid, is perturbed in the epileptogenic hippocampus, particularly in MTLE. We hypothesize that the loss of MCT1 on brain microvessels is mechanistically involved in the pathophysiology of drug-resistant TLE, and propose that re-expression of MCT1 may represent a novel therapeutic approach for this disease.
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DOI：
10.1152/ajpendo.1997.273.1.e207
发表时间：
1997-07-01
影响因子：
5.1
作者：
Gerhart, DZ;Enerson, BE;Drewes, LR
通讯作者：
Drewes, LR
影响因子：
5.6
作者：
Kanemoto, K;Kawasaki, J;Nishimura, M
通讯作者：
Nishimura, M
DOI：
10.1016/j.ejpb.2008.05.022
发表时间：
2008-10-01
影响因子：
4.9
作者：
Fischer, Wiebke;Praetor, Katrin;Brandsch, Matthias
通讯作者：
Brandsch, Matthias
DOI：
10.1016/0005-2736(76)90120-6
发表时间：
1976-01-01
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
CREMER, JE;BRAUN, LD;OLDENDORF, WH
通讯作者：
OLDENDORF, WH
DOI：
10.1152/ajpendo.1998.275.3.e516
发表时间：
1998-09-01
影响因子：
5.1
作者：
Koehler-Stec, EM;Simpson, IA;Landschulz, WH
通讯作者：
Landschulz, WH