Alisky Joseph M, van de Wetering Christopher I, Davidson Beverly L
Department of Internal Medicine, Program in Gene Therapy, University of Iowa College of Medicine, Iowa City, IA 55242, USA.
Exp Neurol. 2002 Nov;178(1):139-46. doi: 10.1006/exnr.2002.8031.
We have discovered novel transport properties of cholera toxin subunit b beyond well-known anterograde and retrograde axonal transport. Injection of 1500 microg 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 microg 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 amyotrophic lateral sclerosis, diabetic neuropathy, motor neuronopathic lysosomal storage diseases, and other neurodegenerative disorders.
我们发现了霍乱毒素B亚基（CTb）除了众所周知的顺行和逆行轴突运输之外的新型运输特性。在年轻成年小鼠中腹腔内或静脉内注射1500微克CTb，导致脑干和脊髓各级运动核（动眼神经核、滑车神经核、展神经核、面神经核、三叉神经核、迷走神经核、舌下神经核、颈核和腰核）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，最后区有大量标记，并且在室周和视上丘脑核中有许多标记神经元。在舌内肌肉注射500微克CTb也能在更有限的范围内产生运动、感觉和下丘脑神经元的普遍标记。外周给予的CTb被神经元摄取，这可能作为一种研究工具有用，或者当与治疗性肽、酶、生长因子或基因治疗载体融合时，可能在肌萎缩侧索硬化症、糖尿病性神经病变、运动神经元病性溶酶体贮积病和其他神经退行性疾病中得到应用。
