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

In the present study, a comparison of potency between a commercially availa ble immunotoxin, 192-immunoglobulin-SAP (192-IgG), and a novel immunotoxin produced in our laboratory, anti-p75-anti-mouse IgG-trichosanthin conjugate s (p75-TCS), was conducted. Both of the immunotoxins were specific for nerv e growth factor p75 receptor. Cholinergic neurons in the rat basal forebrai n and in the neostriatum were depleted after the injection of either 192-Ig G 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 adm inistration. The 192-IgG was more potent than the p75-TCS in the case of ve ntricular injections. In case of striatal injections, 192-IgG caused seriou s tissue necrosis and considerable tissue damage in the brain region. In co ntrast, p75-TCS was potent and caused a selective and specific depletion of cholinergic neurons in the neostriatum. These results indicate that indire ct immunotoxins may be more useful for performing immunolesioning experimen ts in case of brain parenchyma administration. (C) 1999 Elsevier Science B. V. All rights reserved.