Neurotoxic effects, mechanisms, and outcome of 192-IgG saporin

Abstract

The first type-selective anti-neuronal active in vivo immunotoxin is 192 IgG- saporin. 192 IgG-saporin selectively destroys cholinergic neurons of basal forebrain that provide cholinergic input to the hippocampus, entire cortical mantle, amygdala, and olfactory bulb. Immunotoxic lesions by 192 IgG-saporin represent a valid animal model of Alzheimer's disease, given the degeneration of basal cholinergic system present in this pathology. Selective lesioning of cholinergic innervation by means of intracerebroven- tricular (i.c.v.) or intraparenchymal (i.pr.) 192 IgG-saporin is able to interfere with experience-dependent plasticity. A number of studies have demonstrated alteration of several structural and biochemical parameters related with neuroplasticity (dendritic spines and branching of pyramidal neurons, adult neurogenesis, levels of neurotrophic factors) in both cortical mantle and hippocampus. Furthermore, lesions of the cholinergic basal forebrain affect cognitive functions, such as learning, memory, and attention, as well as sleep-waking cycle. The effects of selective immunotoxic lesions have been examined in a variety of behavioral paradigms of learning and memory. The general framework has to take into account the route of injection (i.c.v. or i.pr.), lesion extent, age of lesioning, and kind of behavior analyzed. Namely, cholinergic depletion can elicit specific learning and memory impairments as well as deficits in attentional and discriminative abilities. However, 192 IgG-saporin lesions result in overt behavioral deficits only using high demanding tasks and following highgrade CBF lesions, indicating that the relationship between CBF lesion extent and cognitive impairment is a threshold relationship in which a high degree of neuronal loss can be tolerated without detectable consequences.