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Neurotoxic Effects, Mechanisms, and Outcome of 192-IgG Saporin

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Handbook of Neurotoxicity

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 intracerebroventricular (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 high-grade 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.

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Abbreviations

ACh:

Acetylcholine

AChE:

Acetylcholine esterase

AD:

Alzheimer’s disease

AF64A:

Aziridinium ion of ethylcholine mustard

AMPA:

Aminomethylphosphonate

APP:

Amyloid precursor protein

BDNF:

Brain-derived neurotrophic factor

CBF:

Cholinergic basal forebrain

ChAT:

Choline acetyltransferase

DBBv:

Diagonal band of Broca

DMTP:

Delayed matching to position

DMTS:

Delayed matching to sample

DNMTP:

Delayed nonmatching to position

GABA:

Gamma-aminobutyric acid

HAChT:

High-affinity choline transport

i.c.v.:

Intracerebroventricular

i.pr.:

Intraparenchymal

MS:

Medial septal nucleus

MWM:

Morris Water Maze

NBM:

Nucleus basalis magnocellularis

NGF:

Nerve growth factor

NMDA:

N-methyl-d-aspartate

OF:

Open field

p75:

p75NGFFR, nerve growth factor receptor

PA:

Passive avoidance

RAM:

Radial arm maze

RIPs:

Ribosome-inactivating proteins

SI:

Substantia innominata

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Authors and Affiliations

  1. Department of Psychology, Sapienza University of Rome, Via dei Marsi 78, 00185, Rome, Italy

    Laura Petrosini & P. De Bartolo

  2. I.R.C.C.S. Santa Lucia Foundation, Rome, Italy

    Laura Petrosini, P. De Bartolo & D. Cutuli

Authors
  1. Laura Petrosini
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  2. P. De Bartolo
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  3. D. Cutuli
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Correspondence to Laura Petrosini .

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  1. Department of Biomedical Sciences, East Tennessee State University, Johnson City, Tennessee, USA

    Richard M. Kostrzewa

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Petrosini, L., De Bartolo, P., Cutuli, D. (2014). Neurotoxic Effects, Mechanisms, and Outcome of 192-IgG Saporin. In: Kostrzewa, R. (eds) Handbook of Neurotoxicity. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5836-4_79

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