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White matter neuron biology and neuropathology in schizophrenia.
npj Schizophrenia ( IF 5.4 ) Pub Date : 2019-07-08 , DOI: 10.1038/s41537-019-0078-8
Ryan J Duchatel 1, 2 , Cynthia Shannon Weickert 3, 4, 5 , Paul A Tooney 1, 2
Affiliation  

Schizophrenia is considered a neurodevelopmental disorder as it often manifests before full brain maturation and is also a cerebral cortical disorder where deficits in GABAergic interneurons are prominent. Whilst most neurons are located in cortical and subcortical grey matter regions, a smaller population of neurons reside in white matter tracts of the primate and to a lesser extent, the rodent brain, subjacent to the cortex. These interstitial white matter neurons (IWMNs) have been identified with general markers for neurons [e.g., neuronal nuclear antigen (NeuN)] and with specific markers for neuronal subtypes such as GABAergic neurons. Studies of IWMNs in schizophrenia have primarily focused on their density underneath cortical areas known to be affected in schizophrenia such as the dorsolateral prefrontal cortex. Most of these studies of postmortem brains have identified increased NeuN+ and GABAergic IWMN density in people with schizophrenia compared to healthy controls. Whether IWMNs are involved in the pathogenesis of schizophrenia or if they are increased because of the cortical pathology in schizophrenia is unknown. We also do not understand how increased IWMN might contribute to brain dysfunction in the disorder. Here we review the literature on IWMN pathology in schizophrenia. We provide insight into the postulated functional significance of these neurons including how they may contribute to the pathophysiology of schizophrenia.



中文翻译:

精神分裂症的白质神经元生物学和神经病理学。

精神分裂症被认为是一种神经发育障碍,因为它通常在大脑完全成熟之前就表现出来,并且也是一种大脑皮层疾病,其中GABA能神经元的缺陷最为突出。虽然大多数神经元位于皮层和皮层下灰质区域,但较小的神经元种群位于灵长类动物的白质区,在较小的程度上位于皮层以下的啮齿动物脑。这些间质白质神经元(IWMNs)已被确定为具有神经元的一般标记[例如,神经元核抗原(NeuN)]和神经元亚型(例如GABA能神经元)的特定标记。精神分裂症中IWMN的研究主要集中于已知在精神分裂症中受影响的皮质区域(例如背外侧前额叶皮层)下方的密度。这些大多数死后大脑研究表明,与健康对照组相比,精神分裂症患者的NeuN +和GABA能IWMN密度增加。IWMNs是否参与精神分裂症的发病机理,还是由于精神分裂症的皮质病理而使IWMNs升高是未知的。我们还不了解IWMN升高可能如何导致该疾病的脑功能障碍。在这里,我们回顾精神分裂症中IWMN病理学的文献。我们提供了对这些神经元的假定功能意义的见解,包括它们如何可能有助于精神分裂症的病理生理。IWMNs是否参与精神分裂症的发病机理,还是由于精神分裂症的皮质病理而使IWMNs升高是未知的。我们还不了解IWMN增加可能如何导致该疾病的脑功能障碍。在这里,我们回顾精神分裂症中IWMN病理学的文献。我们提供了对这些神经元的假定功能意义的见解,包括它们如何可能有助于精神分裂症的病理生理。IWMNs是否参与精神分裂症的发病机理,还是由于精神分裂症的皮质病理而使IWMNs升高是未知的。我们还不了解IWMN升高可能如何导致该疾病的脑功能障碍。在这里,我们回顾精神分裂症中IWMN病理学的文献。我们提供了对这些神经元的假定功能意义的见解,包括它们如何可能有助于精神分裂症的病理生理。

更新日期:2019-07-08
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