Immunolesioning of glutamate receptor GluR1-containing neurons in the rat neostriatum using a novel immunotoxin.
1. To investigate the potency of a novel immunotoxin that is specific for glutamate receptor GluR1, a subunit of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA)-type receptor channel, immunolesioning was performed. 2. A ribosome-inactivating protein, trichosanthin (TCS), was isolated and conjugated to the goat anti-rabbit IgG antibody molecule. The anti-rabbit antibody-TCS complex was preincubated with GluR1-specific rabbit antibody to produce a GluR1-specific immunotoxin. The immunotoxin was unilaterally administered into either the neostriatum or the lateral ventricle of rats. 3. Immunoreactivity for GluR1 or GluR4 was revealed in perfuse-fixed sections of the neostriatum obtained from the lesioned and control animals by immunocytochemistry. After ventricular or striatal injections of the immunotoxin, depletions of GluR1-immunoreactive neurons, the presumed GABAergic interneurons in the neostriatum, were found. Depletions of GluR4-immunoreactive perikarya, the presumed same subpopulation of striatal interneurons, were also found. In addition, no change in the pattern of distribution of immunoreactivity for GluR2 or glial fibrillary acidic protein was found in the lesioned neostriatum. These results indicate that the novel GluR1 immunotoxin is potent and specific. 4. In addition, striatal application of the immunotoxin caused a greater depletion in the number of GluR1-immunoreactive neurons. The present results also indicate that the route of immunotoxin application may be important in producing specific lesions.
Kwok
K H
KH
Department of Biology, Hong Kong Baptist University, Kowloon Tong, China.
Law
K B
KB
Wong
R N
RN
Yung
K K
KK
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D007074:Immunoglobulin G / Q000737:chemistry / Q000633:toxicity; D007150:Immunohistochemistry; D000922:Immunotoxins / Q000737:chemistry / Q000633:toxicity*; D007276:Injections, Intraventricular; D007395:Interneurons / Q000187:drug effects* / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D017072:Neostriatum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000187:drug effects* / Q000378:metabolism; D012399:Rotation; D015978:Trichosanthin / Q000737:chemistry / Q000633:toxicity
D001058:Apomorphine; D005904:Glial Fibrillary Acidic Protein; D007074:Immunoglobulin G; D000922:Immunotoxins; D018091:Receptors, AMPA; D015978:Trichosanthin; C104722:glutamate receptor ionotropic, AMPA 2