我们首次定量并确定了神经肽NPFF在人类大脑皮层和下方白质中的分布模式。要做到这一点,我们研究了n=9例无神经系统疾病和n=22例神经退行性疾病,包括散发性肌萎缩侧索硬化症(ALS,n=8),阿尔茨海默病(AD,n=8),皮克病(PiD,n=3),和精神分裂症(n=3)。NPFF免疫阳性细胞主要位于,但不限于此,在浅表白质中,并构成白质间质细胞亚群(WMIC):在回旋冠中占主导地位的金字塔样和多极躯体,而双相性和卵圆形躯体在沟周围的皮质中占主导地位。它们的稀疏分支轴突无髓鞘,并表现出NPFF阳性珠状静脉曲张。我们发现额叶灰质中NPFF免疫阳性细胞明显减少,扣带回,散发性ALS和晚期AD患者的颞上回比对照组高,与对照组相比,这些患者额回下方和深部白质中的NPFF阳性细胞明显减少。值得注意的是,与对照组相比,AD中海马结构中NPFF阳性细胞的数量也显着降低。在PiD中,与对照组相比,扣带回和额叶回的灰质和白质中NPFF阳性细胞的数量显着降低。在精神分裂症患者中,较低的wNPFF细胞计数在新皮质中是显著的和全球性的(扣带,额叶,颞上回,中间,和下回)。NPFF阳性细胞的确切功能及其与浅表皮质皮质白质U纤维的关系目前尚不清楚。这里,NPFF免疫组织化学和表达表征了人脑中先前未识别的细胞群,从而为研究其生理和病理生理作用提供了新的切入点。
We quantified and determined for the first time the distribution pattern of the neuropeptide NPFF in the human cerebral cortex and subjacent white matter. To do so, we studied n = 9 cases without neurological disorders and n = 22 cases with neurodegenerative diseases, including sporadic amyotrophic lateral sclerosis (ALS, n = 8), Alzheimer\'s disease (AD, n = 8), Pick\'s disease (PiD, n = 3), and schizophrenia (n = 3). NPFF-immunopositive cells were located chiefly, but not exclusively, in the superficial white matter and constituted there a subpopulation of white matter interstitial cells (WMIC): Pyramidal-like and multipolar somata predominated in the gyral crowns, whereas bipolar and ovoid somata predominated in the cortex surrounding the sulci. Their sparsely ramified axons were unmyelinated and exhibited NPFF-positive bead-like varicosities. We found significantly fewer NPFF-immunopositive cells in the gray matter of the frontal, cingulate, and superior temporal gyri of both sporadic ALS and late-stage AD patients than in controls, and significantly fewer NPFF-positive cells in the subjacent as well as deep white matter of the frontal gyrus of these patients compared to controls. Notably, the number of NPFF-positive cells was also significantly lower in the hippocampal formation in AD compared to controls. In PiD, NPFF-positive cells were present in significantly lower numbers in the gray and white matter of the cingulate and frontal gyrii in comparison to controls. In schizophrenic patients, lower wNPFF cell counts in the neocortex were significant and global (cingulate, frontal, superior temporal gyrus, medial, and inferior gyri). The precise functions of NPFF-positive cells and their relationship to the superficial corticocortical white matter U-fibers are currently unknown. Here, NPFF immunohistochemistry and expression characterize a previously unrecognized population of cells in the human brain, thereby providing a new entry-point for investigating their physiological and pathophysiological roles.