Immunolesioning of nerve growth factor p75 receptor-containing neurons in the rat brain by a novel immunotoxin: anti-p75-anti-mouse IgG–trichosanthin conjugates

• Published in: Brain research 1999-11, Vol.846 (2), p.154-163
• Main Authors: Kwok, K.H.H., Law, K.B., Wong, R.N.S., Yung, K.K.L.
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Monoclonal - toxicity; Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - toxicity; Basal forebrain; Behavior, Animal - drug effects; Biological and medical sciences; Choline O-Acetyltransferase - analysis; Cholinergic Agents - toxicity; Cholinergic neuron; Denervation - methods; Development. Senescence. Regeneration. Transplantation; Female; Fundamental and applied biological sciences. Psychology; Immunocytochemistry; Immunoglobulin G - chemistry; Immunoglobulin G - pharmacology; Immunotoxins - toxicity; Injections, Intraventricular; N-Glycosyl Hydrolases; Neostriatum; Neostriatum - cytology; Neostriatum - drug effects; Neurons - chemistry; Neurons - drug effects; Neurons - enzymology; Rats; Rats, Sprague-Dawley; Receptor, Nerve Growth Factor - analysis; Receptor, Nerve Growth Factor - immunology; Ribosome inactivating protein; Ribosome Inactivating Proteins, Type 1; Rotation; Saporins; Trichosanthin - chemistry; Trichosanthin - toxicity; Vertebrates: nervous system and sense organs
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/S0006-8993(99)01999-X

In the present study, a comparison of potency between a commercially available immunotoxin, 192-immunoglobulin-SAP (192-IgG), and a novel immunotoxin produced in our laboratory, anti-p75-anti-mouse IgG-trichosanthin conjugates (p75-TCS), was conducted. Both of the immunotoxins were specific for nerve growth factor p75 receptor. Cholinergic neurons in the rat basal forebrain and in the neostriatum were depleted after the injection of either 192-IgG or p75-TCS. These indicate that both types of immunotoxins are potent and useful in performing immunolesioning experiments. In addition, there were variations in potency among the two immunotoxins in different routes of administration. The 192-IgG was more potent than the p75-TCS in the case of ventricular injections. In case of striatal injections, 192-IgG caused serious tissue necrosis and considerable tissue damage in the brain region. In contrast, p75-TCS was potent and caused a selective and specific depletion of cholinergic neurons in the neostriatum. These results indicate that indirect immunotoxins may be more useful for performing immunolesioning experiments in case of brain parenchyma administration.