192IGG-saporin-induced selective lesion of cholinergic basal forebrain system: neurochemical effects on cholinergic neurotransmission in rat cerebral cortex and hippocampus. 1995

S Rossner, and R Schliebs, and W Härtig, and V Bigl
Paul Flechsig Institute for Brain Research, University of Leipzig, Medical Faculty, Germany.

A novel cholinergic immunotoxin (conjugate of the monoclonal antibody 192IgG against the low-affinity nerve growth factor receptor with the cytotoxin saporin) producing selective lesions of cholinergic neurons in rat basal forebrain was applied to study its effect on hippocampal and cerebral cortical cholinergic neurotransmission. Intracerebroventricular injection of 4 micrograms 192IgG-saporin conjugate resulted in a selective loss of cholinergic cells in the basal forebrain nuclei 1 week after application, which was accompanied by decreased activities of choline acetyltransferase and by reduced high-affinity uptake of [3H]choline into cholinergic nerve terminals in the cerebral cortex and hippocampus, as well as by a significant activation of micro- and to a lesser extent of astroglial cells in the hippocampus, but hardly in the cerebral cortex.. The K(+)-stimulated release of [3H]acetylcholine from cortical and hippocampal slices of immunolesioned rats was found to be markedly decreased 1 week after injection. Cholinergic immunolesion led to enhanced cortical M1-muscarinic acetylcholine receptor numbers, but did not alter muscarinic receptor sensitivity as measured by carbachol-stimulated inositol phosphate production or phorbol ester binding to membrane-bound protein kinase C. In the hippocampal formation differential enhancements in binding levels of M1-muscarinic cholinergic receptor sites in the CA1 region and in the dentate gyrus were observed, whereas the nicotinic and M2-muscarinic receptor subtype are seemingly not affected by the immunotoxin in either of the subfields studied. Cholinergic immunolesioning did not result in any alterations in the hybridization signals for m1 through m4 muscarinic acetylcholine receptor mRNA in any region or layer of the hippocampus. The data suggest that (i) the novel cholinergic immunotoxin 192IgG-saporin is an appropriate tool to mimic cholinergic hypofunction in the hippocampal formation and cerebral cortex, and (ii) selective and specific immunolesion of cholinergic cells in medial septal nuclei differentially affects cholinergic receptors in particular hippocampal subfields.

UI MeSH Term Description Entries
D007150 Immunohistochemistry Histochemical localization of immunoreactive substances using labeled antibodies as reagents. Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D007295 Inositol Phosphates Phosphoric acid esters of inositol. They include mono- and polyphosphoric acid esters, with the exception of inositol hexaphosphate which is PHYTIC ACID. Inositol Phosphate,Phosphate, Inositol,Phosphates, Inositol
D008297 Male Males
D009435 Synaptic Transmission The communication from a NEURON to a target (neuron, muscle, or secretory cell) across a SYNAPSE. In chemical synaptic transmission, the presynaptic neuron releases a NEUROTRANSMITTER that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across ELECTRICAL SYNAPSES. Neural Transmission,Neurotransmission,Transmission, Neural,Transmission, Synaptic
D010275 Parasympathetic Nervous System The craniosacral division of the autonomic nervous system. The cell bodies of the parasympathetic preganglionic fibers are in brain stem nuclei and in the sacral spinal cord. They synapse in cranial autonomic ganglia or in terminal ganglia near target organs. The parasympathetic nervous system generally acts to conserve resources and restore homeostasis, often with effects reciprocal to the sympathetic nervous system. Nervous System, Parasympathetic,Nervous Systems, Parasympathetic,Parasympathetic Nervous Systems,System, Parasympathetic Nervous,Systems, Parasympathetic Nervous
D011869 Radioligand Assay Quantitative determination of receptor (binding) proteins in body fluids or tissue using radioactively labeled binding reagents (e.g., antibodies, intracellular receptors, plasma binders). Protein-Binding Radioassay,Radioreceptor Assay,Assay, Radioligand,Assay, Radioreceptor,Assays, Radioligand,Assays, Radioreceptor,Protein Binding Radioassay,Protein-Binding Radioassays,Radioassay, Protein-Binding,Radioassays, Protein-Binding,Radioligand Assays,Radioreceptor Assays
D011976 Receptors, Muscarinic One of the two major classes of cholinergic receptors. Muscarinic receptors were originally defined by their preference for MUSCARINE over NICOTINE. There are several subtypes (usually M1, M2, M3....) that are characterized by their cellular actions, pharmacology, and molecular biology. Muscarinic Acetylcholine Receptors,Muscarinic Receptors,Muscarinic Acetylcholine Receptor,Muscarinic Receptor,Acetylcholine Receptor, Muscarinic,Acetylcholine Receptors, Muscarinic,Receptor, Muscarinic,Receptor, Muscarinic Acetylcholine,Receptors, Muscarinic Acetylcholine
D011978 Receptors, Nicotinic One of the two major classes of cholinergic receptors. Nicotinic receptors were originally distinguished by their preference for NICOTINE over MUSCARINE. They are generally divided into muscle-type and neuronal-type (previously ganglionic) based on pharmacology, and subunit composition of the receptors. Nicotinic Acetylcholine Receptors,Nicotinic Receptors,Nicotinic Acetylcholine Receptor,Nicotinic Receptor,Acetylcholine Receptor, Nicotinic,Acetylcholine Receptors, Nicotinic,Receptor, Nicotinic,Receptor, Nicotinic Acetylcholine,Receptors, Nicotinic Acetylcholine
D002540 Cerebral Cortex The thin layer of GRAY MATTER on the surface of the CEREBRAL HEMISPHERES that develops from the TELENCEPHALON and folds into gyri and sulci. It reaches its highest development in humans and is responsible for intellectual faculties and higher mental functions. Allocortex,Archipallium,Cortex Cerebri,Cortical Plate,Paleocortex,Periallocortex,Allocortices,Archipalliums,Cerebral Cortices,Cortex Cerebrus,Cortex, Cerebral,Cortical Plates,Paleocortices,Periallocortices,Plate, Cortical
D002794 Choline A basic constituent of lecithin that is found in many plants and animal organs. It is important as a precursor of acetylcholine, as a methyl donor in various metabolic processes, and in lipid metabolism. Bursine,Fagine,Vidine,2-Hydroxy-N,N,N-trimethylethanaminium,Choline Bitartrate,Choline Chloride,Choline Citrate,Choline Hydroxide,Choline O-Sulfate,Bitartrate, Choline,Chloride, Choline,Choline O Sulfate,Citrate, Choline,Hydroxide, Choline,O-Sulfate, Choline

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