DISINTEGRATION OF THE SPATIAL-ORGANIZATION OF BEHAVIOR IN EXPERIMENTAL AUTOIMMUNE DEMENTIA

Experimental autoimmune dementia is a rat model designed to examine th e potential role of anti-cholinergic neurons antibodies in neuronal de generation in dementia and Alzheimer's disease. We have previously sho wn that sera of patients with Alzheimer's disease contain antibodies w hich bind specifically to the high molecular weight neurofilament prot ein of the purely cholinergic electromotor neurons of Torpedo. Product ion of such antibodies in experimental autoimmune dementia rats by pro longed immunization with the Torpedo cholinergic high molecular weight neurofilament subunit results in accumulation of antibodies in the se ptum and hippocampus of the immunized rats, in a marked decrease in th e density of forebrain cholinergic neurons, and in memory deficits. In the present study we characterized the open-field behavior of experim ental autoimmune dementia rats, and examined whether, like in dementia , the spatiotemporal organization of their behavior is impaired. The r esults obtained revealed that experimental autoimmune dementia rats tr avel shorter distances; explore a smaller part of the open-field; and perform less round-trips to the key location-the home base-in referenc e to which their behavior is normally organized. The shrinkage of the explored space and the reduced number of round trips are independent o f the amount of locomotion and represent a deterioration in the organi zation of behavior in time and space. These behavioral changes are spe cific to the anti-cholinergic immune response of experimental autoimmu ne dementia rats as they are not observed in rats which were immunized with chemically heterogeneous high molecular weight neurofilament sub unit. The association of anti-cholinergic high molecular weight neurof ilament subunit antibodies in experimental autoimmune dementia rats wi th derangements in the spatiotemporal organization of their behavior, may replicate pathogenic processes in Alzheimer's disease and supports a role for such antibodies in neuronal degeneration in this disease.