Oomura Y, Sasaki K, Li A, Yoshii H, Fukata Y, Yago H, Kimura H, Tooyama I, Hanai K, Nomura Y
Inst. Bio-Active Sci, Nippon Zoki Pharm. Co., Hyogo.
Neurobiology (Bp). 1995;3(3-4):371-80.
Subcutaneous injection of aFGF once per 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 (F) group were enhanced significantly and while those of the saline (S) group deteriorated. The number of cholinergic neurons was decreased slightly and choline acetyltransferase activity in individual neurons in the medial septum which send monosynaptic terminals to the hippocampus was significantly decreased in the S group, but were more spared in the F group. The MAO-B activity was significantly lower in the F group than in the S group. The respective densities of muscarinic and NMDA receptors and the aFGF receptor, i.e. FGFR-1 in the hippocampus were also significantly higher in the F group than in the S group. 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 S group. However, aFGF administration protected against this reduction in response with age. These results show that aFGF provides protection against impairment of not only learning and memory but also the DTH immunoreactivity in SAMP8, indicating thereby a close relationship between learning-memory and T cell immune function.
从出生后3周开始,每周一次对快速老化小鼠(SAM)P8进行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(F)组的学习记忆和细胞免疫功能显著增强,而生理盐水(S)组的这些功能则恶化。S组中胆碱能神经元数量略有减少,向海马体发送单突触终末的内侧隔单个神经元中的胆碱乙酰转移酶活性显著降低,但F组中该酶活性受影响较小。F组中的单胺氧化酶B(MAO-B)活性显著低于S组。F组海马体中毒蕈碱受体、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S组。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。与第2个月相比,S组在第7个月时两种类型的DTH均降低。然而,给予aFGF可防止这种随年龄增长的反应降低。这些结果表明,aFGF不仅能保护SAMP8的学习记忆功能免受损害,还能保护其DTH免疫反应性,从而表明学习记忆与T细胞免疫功能之间存在密切关系。