Sabbatini M, Mignini F, Venarucci D, Vega J A, Amenta F
Dipartimento di Scienze Farmacologiche e Medicina Sperimentale, Università di Camerino, Italy.
Clin Exp Hypertens. 2001 Jan-Feb;23(1-2):127-41. doi: 10.1081/ceh-100001204.
Neurofilaments (NFP) are components of neuronal cytoskeleton involved primarily in axonal transport and in the regulation of dynamic activities of nerve cells. NFP consist of three subunits denominated high- (200 kDa, NFP-H), intermediate- (160 kDa, NFP-I), and low-molecular weight (68 kDa, NFP-L) neurofilament proteins. Their function and polymerization depends on phosphorylation status, and is regulated by Ca2+ influx. Ca2+ overload enhances degradation of NFP and may compromise axonal transport. An increased susceptibility to ischemia occurs in hypertension, which is also a cause of brain damage. In this study, the expression of phosphorylated NFP (P-NFP) was investigated in the brain of spontaneously hypertensive rats (SHR) using immunohistochemical techniques with antibodies against the phosphorylated epitope of NFP RT-97. Microanatomical analysis included frontal cortex, occipital cortex, hippocampus and cerebellar cortex. The effect of long-term treatment with the dihydropyridine-type Ca2+ antagonist nicardipine on the expression of P-NFP was investigated as well. In hypertension a decreased P-NFP immunoreactivity was observed in frontal and occipital cortex, in the CA1 subfield of hippocampus and in the dentate gyrus, but not in the CA3 subfield of hippocampus or in the cerebellar cortex. Treatment with a daily dose of 3 mg/kg of nicardipine and 10 mg/kg of hydralazine significantly reduced systolic pressure in SHR. The above dose of nicardipine and to a lesser extent a non-hypotensive dose of the compound (0.1 mg/kg/day), but not hydralazine, increased P-NFP immunoreactivity in the cerebral cortex and hippocampus, except the CA3 subfield. The possibility that rescued P-NFP immunoreactivity by treatment with nicardipine depends on improved brain perfusion caused by the compound and/or by countering neuronal Ca2+ overload is discussed.
神经丝蛋白（NFP）是神经元细胞骨架的组成部分，主要参与轴突运输和神经细胞动态活动的调节。NFP由三个亚基组成，分别称为高分子量（200 kDa，NFP-H）、中分子量（160 kDa，NFP-I）和低分子量（68 kDa，NFP-L）神经丝蛋白。它们的功能和聚合作用取决于磷酸化状态，并受钙离子内流调节。钙离子过载会增强NFP的降解，并可能损害轴突运输。高血压患者对缺血的易感性增加，这也是脑损伤的一个原因。在本研究中，使用针对NFP RT-97磷酸化表位的抗体，通过免疫组织化学技术研究了自发性高血压大鼠（SHR）大脑中磷酸化NFP（P-NFP）的表达。微观解剖分析包括额叶皮质、枕叶皮质、海马体和小脑皮质。还研究了二氢吡啶类钙离子拮抗剂尼卡地平长期治疗对P-NFP表达的影响。在高血压患者中，在额叶和枕叶皮质、海马体CA1亚区和齿状回中观察到P-NFP免疫反应性降低，但在海马体CA3亚区或小脑皮质中未观察到。每日剂量为3 mg/kg的尼卡地平和10 mg/kg的肼屈嗪治疗可显著降低SHR的收缩压。上述剂量的尼卡地平以及该化合物的非降压剂量（0.1 mg/kg/天）在较小程度上可增加大脑皮质和海马体（CA3亚区除外）中的P-NFP免疫反应性，但肼屈嗪则无此作用。本文讨论了尼卡地平治疗后P-NFP免疫反应性恢复的可能性是否取决于该化合物改善脑灌注和/或对抗神经元钙离子过载。
