Maldonado-Avilés Jaime G, Wu Qiang, Sampson Allan R, Lewis David A
Department of Neuroscience, University of Pittsburgh, Pennsylvania 15213, USA.
Biol Psychiatry. 2006 Aug 1;60(3):226-34. doi: 10.1016/j.biopsych.2005.10.028. Epub 2006 Feb 7.
Although the somal volume of Nissl-stained deep layer 3 pyramidal cells is reduced in prefrontal cortex area 9 of subjects with schizophrenia, the subset of large pyramidal cells immunoreactive (IR) for nonphosphorylated neurofilament protein (NNFP) is not. Consequently, we hypothesized that the somal volume of another subset of pyramidal cells immunoreactive for neuronal calcium binding protein-1 (Necab-1) is significantly reduced in schizophrenia.
We labeled Necab-1-IR pyramidal neurons using immunoperoxidase techniques and estimated the mean somal volume in deep layer 3 of area 9 in 13 matched pairs of control and schizophrenic subjects. Identical studies were conducted for pyramidal neurons immunoreactive for neuronal nuclear protein (Neu-N), which is present in all neurons.
In subjects with schizophrenia, neither the mean somal volume of Necab-1-IR pyramidal neurons nor of Neu-N-IR pyramidal neurons was significantly different from control subjects. In addition, the mean somal volume of Neu-N-IR cells was larger than that of Nissl-stained cells in both subject groups, and the magnitude of this difference was greater for the subjects with schizophrenia.
These findings suggest that immunoperoxidase techniques are associated with an overestimation of the volume of labeled neurons. This confound appears to interact with disease state, and thus obscures differences between diagnostic groups.
尽管精神分裂症患者前额叶皮质9区经尼氏染色的深层3锥体神经元的胞体体积减小,但对非磷酸化神经丝蛋白(NNFP)免疫反应阳性(IR)的大型锥体神经元亚群并非如此。因此,我们推测,在精神分裂症中,对神经元钙结合蛋白-1(Necab-1)免疫反应阳性的另一锥体神经元亚群的胞体体积会显著减小。
我们使用免疫过氧化物酶技术标记Necab-1免疫反应阳性的锥体神经元,并估计了13对匹配的对照和精神分裂症患者中9区深层3的平均胞体体积。对所有神经元中均存在的对神经元核蛋白(Neu-N)免疫反应阳性的锥体神经元进行了相同的研究。
在精神分裂症患者中,Necab-1免疫反应阳性的锥体神经元和Neu-N免疫反应阳性的锥体神经元的平均胞体体积与对照受试者相比均无显著差异。此外,在两个受试者组中,Neu-N免疫反应阳性细胞的平均胞体体积均大于尼氏染色细胞,且精神分裂症患者组中这种差异的幅度更大。
这些发现表明,免疫过氧化物酶技术与标记神经元体积的高估有关。这种混淆似乎与疾病状态相互作用,从而掩盖了诊断组之间的差异。