Katsel Pavel, Roussos Panos, Pletnikov Mikhail, Haroutunian Vahram
Department of Psychiatry, The Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Department of Psychiatry, The Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Genetics and Genomic Sciences, Icahn Institute for Genomics and Multiscale Biology, The Icahn School of Medicine at Mount Sinai, New York, NY, USA; Mental Illness Research, Education and Clinical Center (MIRECC), James J Peters VA Medical Center, Bronx, NY, USA.
Neurosci Biobehav Rev. 2017 Jun;77:327-339. doi: 10.1016/j.neubiorev.2017.04.003. Epub 2017 Apr 8.
Schizophrenia (SZ) is a severe mental disorder with unknown etiology and elusive neuropathological and neurobiological features have been a focus of many theoretical hypotheses and empirical studies. Current genetic and neurobiology information relevant to SZ implicates neuronal developmental and synaptic plasticity abnormalities, and neurotransmitter, microglial and oligodendrocytes dysfunction. Several recent theories have highlighted the neurovascular unit as a potential contributor to the pathophysiology of SZ. We explored the biological plausibility of a link between SZ and the neurovascular system by examining insights gained from genetic, neuroimaging and postmortem studies, which include gene expression and neuropathology analyses. We also reviewed information from animal models of cerebral angiogenesis in order to understand better the complex interplay between angiogenic and neurotrophic factors in development, vascular endothelium/blood brain barrier remodeling and maintenance, all of which contribute to sustaining adequate regional blood flow and safeguarding normal brain function. Microvascular and hemodynamic alterations in SZ highlight the importance of further research and reveal the neurovascular unit as a potential therapeutic target in SZ.
精神分裂症(SZ)是一种病因不明的严重精神障碍,其难以捉摸的神经病理学和神经生物学特征一直是许多理论假说和实证研究的焦点。目前与精神分裂症相关的遗传和神经生物学信息表明存在神经元发育和突触可塑性异常,以及神经递质、小胶质细胞和少突胶质细胞功能障碍。最近的一些理论强调神经血管单元可能是精神分裂症病理生理学的一个促成因素。我们通过研究从遗传、神经影像学和尸检研究中获得的见解,探讨了精神分裂症与神经血管系统之间联系的生物学合理性,这些研究包括基因表达和神经病理学分析。我们还回顾了来自脑 angiogenesis 动物模型的信息,以便更好地理解血管生成和神经营养因子在发育、血管内皮/血脑屏障重塑和维持中的复杂相互作用,所有这些都有助于维持足够的局部血流并保障正常脑功能。精神分裂症中的微血管和血流动力学改变凸显了进一步研究的重要性,并揭示神经血管单元是精神分裂症潜在的治疗靶点。 (注:原文中“angiogenesis”可能有误,推测可能是“angiogenesis”,意为血管生成)