Widespread dispersal of cholera toxin subunit b to brain and spinal cord neurons following systemic delivery

Widespread dispersal of cholera toxin subunit b to brain and spinal cord neurons following systemic delivery
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DOI:
10.1006/exnr.2002.8031
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发表时间:
2002-11-01
影响因子:
5.3
通讯作者:
Davidson, BL
Davidson, BL
中科院分区:
医学2区
文献类型:
--
作者:
Alisky, JM;van de Wetering, CI;Davidson, BL

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我们发现了霍乱毒素亚单位b的新的运输特性,超越了众所周知的顺行和逆行轴突运输。在幼年小鼠体内或静脉注射1560杯CTB后,脑干和脊髓(动眼、滑车、外展、面部、三叉神经、迷走神经、舌下神经、颈椎和腰椎)各级运动核团的标记普遍增强。三叉神经和脊髓初级传入纤维也有广泛的标记,最后在脑室周围核和下丘脑视上核也有大量标记的神经元。在舌头肌肉注射500杯CTB,也可以在更有限的范围内产生运动神经元、感觉神经元和下丘脑神经元的普遍标记。外周给药的神经元摄取CTB可能是一种有用的研究工具,或者,当融合到治疗性多肽、酶、生长因子或基因治疗载体时,可能会应用于萎缩性侧索硬化症、糖尿病神经病变、运动神经元病理性溶酶体储存疾病和其他神经退行性疾病。(C)2002年埃尔塞维尔科学公司(美国)。
We have discovered novel transport properties of cholera toxin subunit b beyond well-known anterograde and retrograde axonal transport. Injection of 1560 mug of CTb intraperitoneally or intravenously in young adult mice resulted in generalized enhanced labeling of motor nuclei at all levels of the brain stem and spinal cord (oculomotor, trochlear, abducens, facial, trigeminal, vagal, hypoglossal, cervical, and lumbar). There was also extensive labeling of trigeminal and spinal primary afferent fibers, bulk labeling of the area postrema, and finally numerous labeled neurons in the periventricular and supraoptic hypothalamic nuclei. Generalized labeling of motor, sensory, and hypothalamic neurons could also be produced on a more limited scale from intramuscular injections of 500 mug of CTb in the tongue. Neuronal uptake of peripherally administered CTb may be useful as a research tool, or, when fused to therapeutic peptides, enzymes, growth factors, or gene therapy vectors, may have application in anlyotrophic lateral sclerosis, diabetic neuropathy, motor neuronopathic lysosomal storage diseases, and other neurodegenerative disorders. (C) 2002 Elsevier Science (USA).