Romano Jacob, Beni-Adani Liana, Nissenbaum Orlev Levy, Brenneman Douglas E, Shohami Esther, Gozes Illana
Department of Clinical Biochemistry, Sackler Faculty of Medicine, Tel Aviv University, Israel.
J Mol Neurosci. 2002 Feb-Apr;18(1-2):37-45. doi: 10.1385/JMN:18:1-2:37.
The femtomolar-acting eight-amino-acid peptide (NAP), derived from activity-dependent neuroprotective protein (ADNP), provides long-term protection against the deleterious effects of closed head injury (CHI) in mice. Fifteen minutes after injury, mice were divided into two groups, control and NAP-treated and a single subcutaneous injection of NAP or vehicle was administered. A third group served as sham-treated (not subjected to head trauma). Each mouse was assessed for its clinical function, using neurological severity score, at various time intervals following CHI, up to 30-45 d. Total cerebral cortex RNA was prepared from the site of injury of CHI mice, and from parallel regions in peptide-treated and sham brains. RNA was then reversed transcribed to yield radioactive cDNA preparations that were hybridized to Atlas array membranes containing 1200 cDNAs spots. Comparison of sham-treated individual mice showed differential expression levels of at least 15 mRNA species. Furthermore, results indicated that one of the genes that did not change among individuals but specifically increased after CHI and decreased after NAP treatment was the cell surface glycoprotein Mac-1 (CD11B antigen). Thus, Mac-1 is suggested as a marker for the long-term outcome of head injury and as a potential target for NAP protective actions.
源自活性依赖神经保护蛋白（ADNP）的飞摩尔活性八氨基酸肽（NAP）可长期保护小鼠免受闭合性颅脑损伤（CHI）的有害影响。损伤后15分钟，将小鼠分为两组，即对照组和NAP治疗组，并分别皮下注射NAP或赋形剂。第三组作为假手术组（未遭受头部创伤）。在CHI后的不同时间间隔（最长30 - 45天），使用神经严重程度评分对每只小鼠的临床功能进行评估。从CHI小鼠的损伤部位以及肽处理组和假手术组大脑的平行区域制备全脑皮质RNA。然后将RNA逆转录以产生放射性cDNA制剂，将其与含有1200个cDNA斑点的Atlas阵列膜杂交。对假手术组个体小鼠的比较显示至少15种mRNA物种的表达水平存在差异。此外，结果表明，在个体间未发生变化，但在CHI后特异性增加且在NAP治疗后降低的基因之一是细胞表面糖蛋白Mac-1（CD11B抗原）。因此，Mac-1被认为是颅脑损伤长期预后的标志物以及NAP保护作用的潜在靶点。
