von Bartheld C S, Schober A, Kinoshita Y, Williams R, Ebendal T, Bothwell M
Department of Physiology and Biophysics, University of Washington, Seattle 98195.
J Neurosci. 1995 Mar;15(3 Pt 2):2225-39. doi: 10.1523/JNEUROSCI.15-03-02225.1995.
The chicken locus coeruleus contains a population of noradrenergic neurons which express the neurotrophin receptor p75 (von Bartheld and Bothwell, 1992). To determine which neurotrophin may regulate the development of noradrenergic neurons in the chicken locus coeruleus, expression of trk receptors, retrograde transport of neurotrophins, and responses to NGF were examined. P75-expressing noradrenergic neurons were found to project to the basal forebrain. They transport radio-iodinated NGF after injections into this target. The retrograde transport of NGF is specific to the noradrenergic neuronal population as evidenced by double labeling with antibodies against dopamine-beta-hydroxylase. The same neuronal population expresses trkA receptor mRNA. The size of noradrenergic neurons in the locus coeruleus proper, but not in the nucleus subcoeruleus, is significantly increased after injections of NGF into the telencephalon, consistent with the hypothesis that target-derived NGF provides trophic support. Noradrenergic coeruleus neurons are rescued from toxic effects of 6-hydroxydopamine injected into the telencephalon when NGF is injected into the midbrain. NGF has no rescue effect when it is coinjected with 6-hydroxy-dopamine into the telencephalon. In explant or dissociated cultures, noradrenergic coeruleus neurons do not respond to elevated levels of NGF with increased neurite outgrowth. Taken together, these results suggest that NGF plays a role in the development and maintenance of noradrenergic coeruleus neurons in the chick brain. The data also support our previous conclusion that major species differences exist between birds (chicken) and mammals with regard to trophic regulation of presumptive homologous neuronal populations.
鸡的蓝斑中含有一群去甲肾上腺素能神经元，它们表达神经营养因子受体p75（冯·巴特黑尔德和博思韦尔，1992年）。为了确定哪种神经营养因子可能调节鸡蓝斑中去甲肾上腺素能神经元的发育，研究了trk受体的表达、神经营养因子的逆行运输以及对神经生长因子（NGF）的反应。发现表达p75的去甲肾上腺素能神经元投射到基底前脑。向该靶点注射后，它们会运输放射性碘化的NGF。用抗多巴胺-β-羟化酶抗体进行双重标记证明，NGF的逆行运输对去甲肾上腺素能神经元群体具有特异性。同一神经元群体表达trkA受体mRNA。向端脑注射NGF后，蓝斑本身而非蓝斑下核中的去甲肾上腺素能神经元大小显著增加，这与靶源性NGF提供营养支持的假设一致。当向中脑注射NGF时，可使端脑注射6-羟基多巴胺所致的毒性作用下的蓝斑去甲肾上腺素能神经元得到挽救。当NGF与6-羟基多巴胺共同注射到端脑时则没有挽救作用。在器官培养或解离培养中去甲肾上腺素能蓝斑神经元对升高的NGF水平无神经突生长增加的反应。综上所述，这些结果表明NGF在鸡脑中去甲肾上腺素能蓝斑神经元的发育和维持中发挥作用。数据还支持我们之前的结论，即鸟类（鸡）和哺乳动物在假定同源神经元群体的营养调节方面存在主要的物种差异。
