Srivastava N, Granholm A C, Gerhardt G A
Department of Basic Science, and the Rocky Mountain Center for Sensor Technology, University of Colorado Health Sciences Center, Denver 80262, USA.
Exp Neurol. 1997 Jun;145(2 Pt 1):524-35. doi: 10.1006/exnr.1997.6485.
The sprouting capacity of aged noradrenergic neurons of the brain-stem nucleus locus coeruleus (LC) was examined using intraocular transplants of fetal tissues. Fetal hippocampal tissue (E18) and LC tissue (E15) were transplanted together as a double transplant into the anterior chamber of the eye of young adult Fischer 344 rats. The double transplants were allowed to mature for 14-18 months, after which an additional fetal hippocampal transplant was placed next to the LC graft. The triple transplants were monitored for overall growth and vascularization for an additional 2-6 months. Immunohistochemical examinations showed that both young (2-6 months old) and aged (16-24 months old) hippocampal cografts contained a plexus of thin varicose tyrosine hydroxylase (TH)-immunoreactive fibers extending throughout the grafted hippocampal tissues. However, the aged hippocampal grafts contained a denser uniform plexus of TH-positive fibers compared to the young transplants. Immunohistochemistry with synapsin antibodies demonstrated that both the young and the aged hippocampal transplants contained much higher densities of synaptic elements than the LC grafts. In vivo electrochemical measurements of potassium-evoked overflow of norepinephrine (NE) in the grafts showed that similar amounts of NE overflow were detected in both the young and the aged hippocampal grafts. HPLC-EC measurements of NE levels in the grafts revealed that there were similar amounts of NE in the young and the aged grafts, and the grafts did not contain serotonin or dopamine. In summary, the findings of the present study show that aged LC neurons are capable of undergoing collateral sprouting producing a functional NE neuronal system when introduced to an appropriate young target.
利用胎儿组织眼内移植技术，对脑干蓝斑核（LC）中衰老的去甲肾上腺素能神经元的发芽能力进行了检测。将胎儿海马组织（胚胎18天）和LC组织（胚胎15天）作为双重移植体共同移植到成年年轻Fischer 344大鼠的眼前房。双重移植体使其成熟14 - 18个月，之后在LC移植物旁边再植入一个胎儿海马移植体。对三重移植体再进行2 - 6个月的整体生长和血管化监测。免疫组织化学检查显示，年轻（2 - 6个月大）和衰老（16 - 24个月大）的海马联合移植体均含有一个稀疏的曲张型酪氨酸羟化酶（TH）免疫反应性纤维丛，延伸至整个移植的海马组织。然而，与年轻移植体相比，衰老的海马移植体含有更密集且均匀的TH阳性纤维丛。用突触素抗体进行免疫组织化学显示，年轻和衰老的海马移植体中突触元件的密度均远高于LC移植体。对移植物中钾诱发的去甲肾上腺素（NE）溢出进行的体内电化学测量表明，在年轻和衰老的海马移植体中检测到的NE溢出量相似。对移植物中NE水平进行的高效液相色谱 - 电化学检测显示，年轻和衰老移植物中的NE含量相似，且移植物中不含5 - 羟色胺或多巴胺。总之，本研究结果表明，衰老的LC神经元在被引入合适的年轻靶点时，能够进行侧支发芽，产生功能性的NE神经元系统。
