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Cholinergic immunolesions by 192IgG‐saporin—a useful tool to simulate pathogenic aspects of alzheimer's disease
Author(s) -
Roßner Steffen
Publication year - 1997
Publication title -
international journal of developmental neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.761
H-Index - 88
eISSN - 1873-474X
pISSN - 0736-5748
DOI - 10.1016/s0736-5748(97)00035-x
Subject(s) - cholinergic , nucleus basalis , neuroscience , basal forebrain , cholinergic neuron , amyloid precursor protein , alzheimer's disease , acetylcholine , senile plaques , saporin , biology , medicine , endocrinology , immunotoxin , disease , immunology , antibody , monoclonal antibody
Alzheimer's disease, the most common cause of senile dementia, is characterized by intracellular formation of neurofibrillary tangles, extracellular deposits of beta amyloid as well as cerebrovascular amyloid accumulation and a profound loss of cholinergic neurons within the nucleus basalis Meynert with alterations in cortical neurotransmitter receptor densities. The use of the cholinergic immunotoxin 192IgG‐saporin allows for the first time study of the impact of cortical cholinergic deafferentation on cortical neurotransmission, learning, and memory without direct effects on other neuronal sytems. This model also allows the elucidation of contributions of cholinergic mechanisms to the establishment of other pathological features of Alzheimer's disease. The findings discussed here demonstrate that cholinergic immunolesions by 192IgG‐saporin induce highly specific, permanent cortical cholinergic hypoactivity and alterations in cortical neurotransmitter densities comparable to those described for Alzheimer's disease. The induced cortical cholinergic deficit also leads to cortical/hippocampal neurotrophin accumulation and reduced amyloid precursor protein (APP) secretion, possibly reflecting the lack of stimulation of postsynaptic M1/M3 muscarinic receptors coupled to protein kinase C. This immunolesion model should prove useful to test therapeutic strategies based on stimulation of cortical cholinergic neurotransmission or amelioration of pathogenic aspects of cholinergic degeneration in the basal forebrain. Application of the model to animal species that can develop β ‐amyloid plaques could provide information about the contribution of cholinergic function to amyloidogenic APP processing.