Hayashi Yoshitaka, Tatebayashi Yoshitaka
Tokyo Metropolitan Institute of Medical Science, 2-1-6, Kamikitazawa, Setagaya-ku, Tokyo, 156-8506 Japan.
Nihon Shinkei Seishin Yakurigaku Zasshi. 2012 Aug;32(4):211-8.
The neuropathology of psychiatric disorders has long been of interest in psychiatry. Several abnormalities in the prefrontal cortex have been demonstrated in major depressive disorders; however, only a small number of quantitative studies have been conducted, partly because the stereological techniques often used for such investigations are hampered by intrinsically low throughput, typically requiring long periods of time to complete. Recently, we developed a quantitative cell-counting method for frozen unfixed postmortem brains using a flow cytometer. Anisotropic frozen brain tissue was transformed into an isotropic suspension of nuclei; the numbers and fluorescent intensities of 7-AAD(+), a DNA marker, were quantified; and the nuclei were immunolabeled for the neuronal and oligodendroglial nuclear markers, NeuN and olig2, respectively. Using this method, the frontopolar and inferior temporal cortical gray matter of major depressive disorder patients, as well as that of normal controls, was analyzed. We found that the densities of 7-AAD(+) and olig2(+) nuclei in the gray matter tissue of the frontopolar cortex from major depressive disorder subjects were significantly reduced when compared to those from controls, but not in the inferior temporal cortex. Our findings suggest that the pathogenesis of major depressive disorders may involve some abnormalities in cortical myelination in the adult frontopolar cortex.
精神疾病的神经病理学长期以来一直是精神病学关注的焦点。在重度抑郁症中已证实前额叶皮质存在多种异常；然而，仅有少数定量研究，部分原因是常用于此类研究的立体学技术因通量本质上较低而受限，通常需要很长时间才能完成。最近，我们开发了一种使用流式细胞仪对冷冻未固定的死后大脑进行定量细胞计数的方法。将各向异性的冷冻脑组织转化为核的各向同性悬浮液；对DNA标记物7 - AAD(+)的数量和荧光强度进行定量；并分别针对神经元和少突胶质细胞核标记物NeuN和olig2对细胞核进行免疫标记。使用这种方法，对重度抑郁症患者以及正常对照的额极和颞下皮质灰质进行了分析。我们发现，与对照组相比，重度抑郁症受试者额极皮质灰质组织中7 - AAD(+)和olig2(+)核的密度显著降低，但颞下皮质未出现这种情况。我们的研究结果表明，重度抑郁症的发病机制可能涉及成人额极皮质中皮质髓鞘形成的一些异常。
