Depletion of glutamate GluR2 receptor-containing neurons in the rat neostriatum by specific immunotoxin.
In the present study, a novel GluR2 receptor-specific immunotoxin was produced. The immunotoxin was produced by conjugation of molecules of trichosanthin, a ribosome inactivating protein, with goat anti-mouse immunoglobulin molecules. The secondary antibody was then combined with a commercially available GluR2 specific primary antibody to form an immunotoxin. The immunotoxins were unilaterally injected either into the neostriatum or into the lateral ventricle of rats. After one week, ipsilateral turning movements were observed after apomorphine treatments in those animals injected by the striatal route. In perfuse-fixed sections of the neostriatum, immunoreactivity for GluR2 was found to decrease in the striatal-lesioned animals. Most of the GluR2-immunoreactive perikarya in the neostriatum, the presumed medium spiny neurons, were depleted. In addition, immunoreactivity for GluR2/3, GluR5/6/7 and NMDAR1 was found to decrease to a different extent in the lesioned neostriatum. The number of GluR1-immunoreactive perikarya in the neostriatum, a group of striatal interneurons, was not affected by the GluR2 lesion. Ventricular administration of the GluR2 immunotoxin however, was found to be less potent. These results demonstrate for the first time that an indirect immunotoxin is useful for immunolesioning. A difference in potency was also observed in different routes of administration. The depletion of GluR2-containing medium spiny neurons in the neostriatum may upset the balance of the output systems of the basal ganglia and has a profound effect in movement control of the animals.
Kwok
K H
KH
Department of Biology, Hong Kong Baptist University, Kowloon Tong, Hong Kong, People's Republic of China.
Wong
R N
RN
Yung
K K
KK
D000818:Animals; D005260:Female; D007074:Immunoglobulin G / Q000494:pharmacology; D007150:Immunohistochemistry; D000922:Immunotoxins / Q000494:pharmacology*; D007267:Injections; D007276:Injections, Intraventricular; D017072:Neostriatum / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018092:Kainic Acid Receptors / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D012016:Reference Values; D015978:Trichosanthin / Q000494:pharmacology*
D007074:Immunoglobulin G; D000922:Immunotoxins; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D015978:Trichosanthin; C104723:glutamate receptor ionotropic, AMPA 3; C104722:glutamate receptor ionotropic, AMPA 2