Retrograde transport of a traditional Chinese medicine, alpha-trichosanthin, and its selective neural toxicity.
OBJECTIVE
To investigate the peripheral neuronal toxicity of a traditional Chinese medicine, alpha-trichosanthin (TCS).


METHODS
TCS and rhodamine-conjugated TCS were separately injected into the rat sciatic nerve. Saline and rhodamine were used alone and separately as control solutions. The motor neurons in the spinal cord and sensory neurons in the dorsal root ganglia were separately counted. The entry of TCS molecules into neurons was observed under the fluorescence microscope. The glial reactions were studied by lectin staining and immunohistochemical method. The muscles innervated by the sciatic nerve and distal to the injection sites, and the nerves proximal to the injection sites were also collected and examined.


RESULTS
TCS was taken up and transported by peripheral axons, and at a dose of 1 nmol, killed more than 90% of the motor neurons in 5 days, but only one-third of the sensory neurons of the injected nerve. The loss of neurons was permanent, while the increase of glial activities was mild and transient.


CONCLUSIONS
TCS is retrogradely transported by axons of the injected nerve. TCS shows a selective neurotoxicity on different types of neurons. Hence TCS is useful in producing neural lesion in research, and this use may also be of applicational value in treating chronic spasticity, hyperalgesia, and pain.
Shen
Wei-Zai
WZ
School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR, China.
Sha
Ou
O
Yew
David Tai-Wai
DT
Kwong
Wing-Hang
WH
D000020:Abortifacient Agents, Nonsteroidal / Q000378:metabolism* / Q000633:toxicity; D000818:Animals; D001369:Axons / Q000378:metabolism; D001692:Biological Transport; D005260:Female; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism; D007150:Immunohistochemistry; D008516:Medicine, Chinese Traditional; D008856:Microscopy, Fluorescence; D009046:Motor Neurons / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012235:Rhodamines / Q000737:chemistry; D012584:Sciatic Nerve / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000187:drug effects* / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D015978:Trichosanthin / Q000378:metabolism* / Q000633:toxicity
D000020:Abortifacient Agents, Nonsteroidal; D012235:Rhodamines; D015978:Trichosanthin; C027755:rhodamine isothiocyanate