Widespread dispersal of cholera toxin subunit b to brain and spinal cord neurons following systemic delivery.
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.
Alisky
Joseph M
JM
Department of Internal Medicine, Program in Gene Therapy, University of Iowa College of Medicine, Iowa City, IA 55242, USA.
van de Wetering
Christopher I
CI
Davidson
Beverly L
BL
D000276:Adjuvants, Immunologic / Q000493:pharmacokinetics*; D000818:Animals; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002772:Cholera Toxin / Q000493:pharmacokinetics*; D007273:Injections, Intramuscular; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009046:Motor Neurons / Q000378:metabolism; D009475:Neurons, Afferent / Q000378:metabolism; D013116:Spinal Cord / Q000166:cytology / Q000378:metabolism*
D000276:Adjuvants, Immunologic; D002772:Cholera Toxin