Bäckman C, Biddle P T, Ebendal T, Friden P M, Gerhardt G A, Henry M A, Mackerlova L, Söderström S, Strömberg I, Walus L
Department of Basic Science, University of Colorado HSC, Denver, USA.
Exp Neurol. 1995 Mar;132(1):1-15. doi: 10.1016/0014-4886(95)90037-3.
The purpose of this study was to investigate the effects of nerve growth factor (NGF) conjugated to a monoclonal transferrin receptor antibody (OX-26) on septal transplants in oculo. Three different doses of OX-26-NGF conjugate (0.3, 3, and 50 micrograms/injection) were injected into the tail vein of young adult hosts 2, 4, and 6 weeks following intraocular transplantation of fetal forebrain tissue containing septal nuclei. Intravenous injections of OX-26 alone, NGF alone, and saline served as controls. An increase in intraocular tissue growth, as well as an increase in the intensity of immunoreactivity for p75 receptors and acetylcholinesterase, was observed following peripheral OX-26-NGF administration at the two highest doses tested. In addition, aged host rats with 16-month-old intraocular septal grafts were injected intravenously with OX-26 or OX-26-NGF (10 micrograms NGF/injection) every 2 weeks until the transplants were 24 months old. The intensity of choline acetyltransferase-like (ChAT) staining appeared to be greater and the cell bodies were larger with more processes in aged transplants in hosts treated with the OX-26-NGF conjugate than in aged OX-26-treated subjects. The present results suggest that peripheral OX-26-NGF can deliver biologically active NGF across the blood-brain barrier and have dose-dependent positive effects on both aged and developing cholinergic neurons in septal transplants.
本研究的目的是调查与单克隆转铁蛋白受体抗体(OX-26)偶联的神经生长因子(NGF)对眼内隔移植的影响。在含有隔核的胎儿前脑组织眼内移植后2、4和6周,将三种不同剂量的OX-26-NGF偶联物(0.3、3和50微克/注射)注入年轻成年宿主的尾静脉。单独静脉注射OX-26、单独注射NGF和注射生理盐水作为对照。在测试的两个最高剂量下,外周给予OX-26-NGF后,观察到眼内组织生长增加,以及p75受体和乙酰胆碱酯酶免疫反应强度增加。此外,对眼内有16个月大隔移植的老年宿主大鼠,每2周静脉注射一次OX-26或OX-26-NGF(10微克NGF/注射),直至移植组织24个月大。与接受OX-26治疗的老年受试者相比,接受OX-26-NGF偶联物治疗的老年宿主中,隔移植组织中胆碱乙酰转移酶样(ChAT)染色强度似乎更大,细胞体更大,突起更多。目前的结果表明,外周给予OX-26-NGF可以使生物活性NGF穿过血脑屏障,对隔移植中衰老和发育中的胆碱能神经元具有剂量依赖性的积极作用。