Oomura Y, Sasaki K, Li A, Yoshii H, Fukata Y, Yago H, Kimura H, Tooyama I, Hanai K, Nomura Y, Yanaihara N
Institute of Bio-Active Science, Nippon Zoki Pharmaceutical Co., Hyogo, Japan.
Ann N Y Acad Sci. 1996 Jun 15;786:337-47. doi: 10.1111/j.1749-6632.1996.tb39075.x.
Subcutaneous injection of aFGF once a week into senescence-accelerated mice (SAM)P8 was begun at 3 weeks after birth and continued for 10 months. Saline was injected as a control. Learning and memory and cellular immunological functions in the aFGF group were enhanced significantly, while those of the saline group deteriorated. 1. The number of cholinergic neurons was decreased by less than 20% and choline acetyltransferase activity in individual neurons in the medical septum which send monosynaptic terminals to the hippocampus was significantly decreased in the saline group, but not so much in the aFGF group. 2. The respective densities of muscarinic and NMDA receptors and the aFGF receptor, i.e., FGFR-1 on the hippocampal neurons were also significantly higher in the aFGF group than in the saline group. 3. The long-term potentiation in the hippocampal slice preparations after a brief tetanic stimulation at the Schaffer collateral/commissural afferents was significantly facilitated in the aFGF group, but not in the saline group. 4. These data indicate the normalization caused by aFGF of the medial septohippocampal circuit, which is necessary for learning and memory. 5. The delayed type hypersensitivity reactions (DTH) in the footpad caused by challenge with trinitrophenyl or sheep red blood cells as measured at the end of the 2nd and 7th months, indicated the T cell immune response. Both types of DTHs were reduced in the 7th month as compared with the 2nd month in the saline group, but the aFGF group was protected against this reduction in accordance with age. 6. These results show that aFGF provides protection against impairment of not only learning and memory but also DTH immunoreactivity in SAMP8. They also indicate a close relationship between learning and memory and T cell immune function.
从出生后3周开始，每周一次向快速老化小鼠（SAM）P8皮下注射碱性成纤维细胞生长因子（aFGF），持续10个月。注射生理盐水作为对照。aFGF组的学习记忆和细胞免疫功能显著增强，而生理盐水组的功能则恶化。1. 生理盐水组中，向海马发送单突触终末的内侧隔区中胆碱能神经元数量减少不到20%，单个神经元中的胆碱乙酰转移酶活性显著降低，但aFGF组的降低程度没那么大。2. aFGF组海马神经元上毒蕈碱受体、N-甲基-D-天冬氨酸（NMDA）受体以及aFGF受体（即FGFR-1）的各自密度也显著高于生理盐水组。3. 在aFGF组中，在Schaffer侧支/联合传入纤维处进行短暂强直刺激后，海马脑片制备中的长时程增强显著易化，但生理盐水组没有。4. 这些数据表明aFGF使内侧隔海马回路正常化，而这对于学习和记忆是必需的。5. 在第2个月末和第7个月末测量的由三硝基苯或绵羊红细胞激发引起的足垫迟发型超敏反应（DTH）表明了T细胞免疫反应。在生理盐水组中，与第2个月相比，两种类型的DTH在第7个月都降低了，但aFGF组随年龄增长免受这种降低的影响。6. 这些结果表明，aFGF不仅能保护SAMP8的学习记忆和DTH免疫反应性免受损害。它们还表明学习记忆与T细胞免疫功能之间存在密切关系。
