Neurotoxic effects, mechanisms and outcome of 192 IgG-Saporin Lesions

The first type-selective anti-neuronal active in vivo immunotoxin is the 192 IgG-saporin. 192 IgG-saporin selectively destroys basal forebrain cholinergic neurons 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. The selective lesioning of cholinergic innervation by means of 192 IgG-saporin (injected i.p. or i.c.v.) is able to interfere with experience-dependent plasticity. A number of studies have demonstrated alterations of several structural and biochemical parameters related to neuroplasticity (dendritic spines and branching of pyramidal neurons, adult neurogenesis, levels of neurotrophic factors, neurotransmission, microglia density) 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 route of injection (i.c.v. or i.p.), lesion extent, age of lesioning, and kind of behavior analyzed. However, 192 IgG-saporin lesions result in a quite unexpected behavioral picture: in fact, massive cholinergic depletion elicits little or no impairment in spatial and nonspatial learning and memory functions and conversely, deficits in attentional and discriminative abilities.