Morphometric analysis of the cerebral expression of ATP-binding cassette transporter protein ABCB1 in chronic schizophrenia: Circumscribed deficits in the habenula
Morphometric analysis of the cerebral expression of ATP-binding cassette transporter protein ABCB1 in chronic schizophrenia: Circumscribed deficits in the habenula
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DOI：
10.1016/j.schres.2016.02.036
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发表时间：
2016-11-01
影响因子：
4.5
通讯作者：
Pahnke, Jens
中科院分区：
文献类型：
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作者：
Bernstein, Hans-Gert;Hildebrandt, Jens;Pahnke, Jens
越来越多的证据表明，微血管异常和血脑屏障（BBB）功能障碍显着有助于精神分裂症的病理生理。ATP结合盒转运体ABCB 1是完整BBB的重要分子组成部分，其与许多神经退行性疾病和精神疾病（包括精神分裂症）有关。然而，ABCB 1在精神分裂症中的区域和细胞表达尚未探索。因此，我们研究了ABCB1蛋白表达的化学方法在12个人类死后的大脑区域，已知发挥作用，在精神分裂症，在13例精神分裂症患者和9个控制。在研究的12个脑区中，有10个脑区的ABCB 1表达毛细血管的数密度在所有精神分裂症患者和对照组之间没有显着差异。然而，精神分裂症患者的左右缰复合体毛细血管密度显著降低。此外，我们发现在左侧缰核中表达ABCB 1的神经元的密度显著降低。在缰毛细血管ABCB 1表达减少可能有助于增加脑水平的促炎细胞因子在精神分裂症患者，而减少这种蛋白质的表达在内侧缰神经元（这可能是嘌呤能）的亚群可能与异常的嘌呤及其受体在这种疾病中发现。(C)2015 Elsevier B.V.版权所有。
There is increasing evidence that microvascular abnormalities and malfunction of the blood-brain barrier (BBB) significantly contribute to schizophrenia pathophysiology. The ATP-binding cassette transporter ABCB1 is an important molecular component of the intact BBB, which has been implicated in a number of neurodegenerative and psychiatric disorders, including schizophrenia. However, the regional and cellular expression of ABCB1 in schizophrenia is yet unexplored. Therefore, we studied ABCB1 protein expression immunohistochemically in twelve human post-mortem brain regions known to play a role in schizophrenia, in 13 patients with schizophrenia and nine controls. In ten out of twelve brain regions under study, no significant differences were found with regard to the numerical density of ABCB1-expressing capillaries between all patients with schizophrenia and control cases. The left and right habenular complex, however, showed significantly reduced capillary densities in schizophrenia patients. In addition, we found a significantly reduced density of ABCB1-expressing neurons in the left habenula. Reduced ABCB1 expression in habenular capillaries might contribute to increased brain levels of proinflammatory cytokines in patients with schizophrenia, while decreased expression of this protein in a subpopulation of medial habenular neurons (which are probably purinergic) might be related to abnormalities of purines and their receptors found in this disease. (C) 2015 Elsevier B.V. All rights reserved.