Intrastriatal and intraventricular infusion of brain-derived neurotrophic factor in the cynomologous monkey: Distribution, retrograde transport and co-localization with substantia nigra dopamine-containing neurons
Intrastriatal and intraventricular infusion of brain-derived neurotrophic factor in the cynomologous monkey: Distribution, retrograde transport and co-localization with substantia nigra dopamine-containing neurons
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DOI：
10.1016/0306-4522(95)00431-9
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发表时间：
1996-03-01
期刊：
影响因子：
3.3
通讯作者：
Kordower, JH
中科院分区：
文献类型：
--
作者：
Mufson, EJ;Kroin, JS;Kordower, JH
使用磁共振成像引导立体定位脑室内和纹状体内输注检查食蟹猴脑源性神经营养因子的分布和逆行运输。两只脑室内动物以3μg/h的剂量输注脑源性神经营养因子21天和28天。第三只脑室内动物使用 Alzet 2002 微型泵依次接受 15、30 和 60 μg/h 脑源性神经营养因子的连续输注，持续 7 天。对于多只纹状体动物（n = 5），每个部位注射剂量为 3 μg/h。一只纹状体猴被注射 10 mM 磷酸盐缓冲盐水（pH 7.4）的载体溶液 14 天，结果没有脑源性神经营养因子免疫反应性。较低剂量的脑室内输注后，脑源性神经营养因子的免疫反应性仅限于心室室管膜层。在序贯较高剂量脑室内病例中，尽管室管膜壁和邻近尾状核受到损伤，但插管主要位于侧脑室内。脑源性神经营养因子免疫反应性显示注射液在同侧扩散，并在较小程度上扩散到对侧尾状核、隔膜、眶皮层和室管膜壁。在这种情况下，在束旁丘脑和黑质、致密部以及皮质、对角带垂直肢和基底核内发现了逆行标记的脑源性神经营养因子神经元。脑源性神经营养因子纹状体内输注逆行标记感觉运动皮层、束旁丘脑和黑质、致密部内的核周。这些病例的切片对脑源性神经营养因子和酪氨酸羟化酶（多巴胺的合成酶）进行双重免疫反应，揭示了致密部多巴胺能神经元的亚群，其中含有逆行转运的脑源性神经营养因子。这些发现表明，在灵长类动物中，黑质多巴胺神经元的选定亚群逆行转运脑源性神经营养因子。此外，在正常和神经病理状态下，选定的黑质细胞是否对脑源性神经营养因子的营养影响有反应仍有待确定。
The distribution and retrograde transport of brain-derived neurotrophic factor was examined using magnetic resonance imaging guided stereotaxic intracerebroventricular and intrastriatal infusion in the cynomologous monkey. Two intracerebroventricular animals were infused with brain-derived neurotrophic factor at a dose of 3 mu g/h for 21 and 28 days. A third intracerebroventricular animal received sequential infusions of 15, 30 and 60 mu g/h brain-derived neurotrophic factor each for seven days using an Alzet 2002 minipump. For the multiple intrastriatal animals (n = 5) a dose of 3 mu g/h was infused into each site. One intrastriatal monkey was infused with vehicle solution of 10 mM phosphate-buffered saline pH 7.4 for 14 days resulting in no brain-derived neurotrophic factor immunoreactivity. Following the lower dose intracerebroventricular infusion, brain-derived neurotrophic factor immunoreactivity was confined to the ventricular ependymal layer. In the sequential higher dose intracerebroventricular case, the cannula was located mainly within the lateral ventricle, although there was damage to the ependymal wall and adjacent caudate nucleus. Brain-derived neurotrophic factor immunoreactivity revealed spread of injectate within the ipsilateral and to a lesser extent the contralateral caudate nucleus, septum, orbital cortex and ventricular ependymal wall. In this case, retrogradely labelled brain-derived neurotrophic factor neurons were found within the parafascicular thalamus and substantia nigra, pars compacta, as well as within cortex, vertical limb of the diagonal band and nucleus basalis. Brain-derived neurotrophic factor intrastriatal infusion retrogradely labelled perikarya within sensory motor cortex, parafascicular thelamus and substantia nigra, pars compacta. Sections from these cases dual-immunoreacted for brain-derived neurotrophic factor and tyrosine hydroxylase, the synthesizing enzyme for dopamine, revealed a subpopulation of pars compacta dopaminergic neurons which contained retrogradely transported brain-derived neurotrophic factor.These findings indicate that a select subgroup of nigral dopamine neurons retrogradely transport brain-derived neurotrophic factor in the primate. Furthermore it remains to be determined whether select nigral cells are responsive to the trophic influences of brain-derived neurotrophic factor in the normal and neuropathologic condition.