Change of the gene for brain-derived neurotroplud factor (BDNF) in the primate brain during aging

研究了恒河猴衰老过程中脑源性神经营养因子(BDNF)和生长抑素(SRIF)基因的表达。脑源性神经营养因子基因在不同脑区表达下降(4.0kb转录本为20-50%，1.6kb转录本为40-70%)。在海马区，1.6kb的mRNA水平在30岁时下降到2岁时的60%。在海马区和几个脑区，SRIF基因表达显著降低(60%-70%)。BDNF可增强SRIF基因的表达，提示BDNF基因表达的降低可能导致灵长类动物脑内SRIF基因表达水平随增龄而下降。(Brain Res.1997)2.TrkB是一种神经营养因子的受体，如BDNF.TrkB基因产生全长蛋白(TK+)和缺乏酪氨酸激酶结构域的截短形式(TK-)。用免疫组织化学方法研究了胚胎140d至成年期恒河猴海马区的TK+免疫反应结构。从胚胎期到成年期，在齿状回颗粒细胞、杏仁角锥体细胞和下丘脑锥体细胞中观察到TK+免疫反应阳性，提示TK+可能参与了猴海马区的形成和维持。结果1997)经Western印迹分析，在发育中的猴大脑皮质中，TK+在胚胎期120天至成年期均有表达。相反，TK-在出生后表达增加，这表明TK-在灵长类动物大脑中作为TK+的负效应因子发挥着重要作用，降低了发育过程中对BDNF的反应性。神经科。ABS.，1997)

The expression of the genes for brain-derived neurotrophic factor (BDNF) and somatostatin (SRIF) was investigated in the brain of the macaque monkey during the aging process (2years, 10years, and>30years). BDNF mRNA declined (20-50% for 4.0kb transcript, and 40-70% for the 1.6kb transcript) in the various cerebral subdivisions. In the hippocampus, the level of the 1.6kb mRNA at > 30 years old declined to 60% of the level at 2 years old. SRIF mRNA significantly decreased (60%-70%) in the hippocampus and in several carebral subdivisions. The expression of SRIF mRNA has been shown to be enhanced by BDNF,suggesting the decrease in gene expression of BDNF may cause the levels of SRIF mRNA to decline in the primate brain during aging. (Brain Res.1997)2.TrkB is a receptor for neurotrophins such as BDNF.The trkB gene give rise to the full length protein (TK+) and the truncated form (TK-) that lacks the tyrosin kinase domain. The TK+ immunoreactive structures were investigated in the monkey hippocampal formation between embryonic day 140 and adult stage. TK+ immunoreactivity was observed from the embryonic period to the adult stage in the granule cells of the dentate gyrus, the pyramidal cells of Ammon's horn and of the subiculum, indicating that TK+ may participate in the formation and the maintenance of the monkey hippocampus.(Neurosci. Res. 1997) By the western blot analysis, TK+ was detected at the same levels from embryonic 120 days to adult period in the developing monkey cerebral cortices. In contrast, the expression of TK- increased after the new-born stage, suggesting that TK- plays an important role as a negative effector of TK+ in the primate brain, reducing responsiveness to BDNF during development.(Soc. Neurosci. Abs., 1997)