Perinatal 192 IgG-Saporin as Neuroteratogen

Abstract

The immunotoxin 192 IgG-saporin selectively destroys basal forebrain cholinergic neurons that provide cholinergic input to the hippocampus, entire cortical mantle, amygdala, and olfactory bulb. Perinatal immunotoxic lesions by 192 IgG-saporin induce long-lasting cholinergic depletion mimicking a number of developmental disorders reported in humans. The perinatal injection of 192 IgG-saporin induces several brain modifications, which are observed in neocortex and hippocampus at short and long term. These plastic changes involve both structural (alterations in brain volume, neuronal morphology, and neurogenesis) and molecular (modulations of the levels of neurotransmitters and other proteins related to neurodegeneration) levels. Moreover, the perinatal injection of 192 IgG-saporin may interact with the brain plastic capacity to react to other injuries. Perinatal 192 IgG-saporin lesions allowed investigating the role of the basal forebrain cholinergic system in modulating behavioral functions in developing as well as adult rats. After perinatal cholinergic depletion, rats display reduced ultrasonic vocalizations as neonates, learning and exploratory deficits as juveniles, altered discriminative abilities, impulsive and perseverative behaviors, and memory deficits as adults. Overall, these findings underline the importance of cholinergic system integrity for the development of specific structural and functional features.

Neuroprotective Role of Dietary Supplementation with Omega-3 Fatty Acids in the Presence of Basal Forebrain Cholinergic Neurons Degeneration in Aged Mice

“…To address this issue, in the present study we investigated whether a pre-treatment with n-3 PUFA was able to prevent behavioral and/or morphological deficits induced by basal forebrain cholinergic depletion in aged mice. The immunotoxic lesion of the basal forebrain through saporin provides a valid animal model to partially mimic AD pathology by provoking a selective and permanent removal of basal forebrain cholinergic inputs to the hippocampus, the entire cortical mantle, the amygdala and the olfactory bulb [13]. Overall, here we found that n-3 PUFA pre-treatment was effective in counteracting some functional and morphological deficits induced by the cholinergic depletion.…”

“…In the past three decades, the availability of saporin immunotoxins allowed studying the role of basal forebrain cholinergic system in several cognitive functions and its implications in aging and dementia [11][12][13]. In fact, saporin immunotoxins selectively cause death of cholinergic cells by inhibiting ribosomal protein synthesis when it is taken up into cells expressing the low-affinity p75 neurotrophin receptor [11,14,15].…”

Behavioral, neuromorphological, and neurobiochemical effects induced by omega-3 fatty acids following basal forebrain cholinergic depletion in aged mice

“…injection of the mu-p75-saporin (saporin) immunotoxin is a valid animal model to partially mimic early AD pathology in mice, since the loss of integrity of the basal forebrain cholinergic system is one of the most reliable hallmarks of AD pathology [53]. Namely, the saporin immunotoxin provokes a selective and permanent removal of basal forebrain cholinergic inputs to the hippocampus, the entire cortical mantle, the amygdala, and the olfactory bulb [54][55][56].…”