Decrease of GABAergic markers and arc protein expression in the frontal cortex by intraventricular 192 IgG-saporin.

Abstract

BACKGROUND/AIMS:

Previous studies used 192 IgG-saporin to study cholinergic function because of its facility for selective lesioning; however, results varied due to differences in the methods of administration and behavioral tests used. We examined an animal model of dementia using 192 IgG-saporin to confirm its features before applying this model to research of therapeutic drugs or electrical stimulation techniques.

METHODS:

Features were verified by the Morris water maze test, immunochemistry, and Western blotting. Animals were examined after intraventricular injection of 192 IgG-saporin (0.63 μg/μl; 6, 8, and 10 μl) or phosphate-buffered saline.

RESULTS:

In the acquisition phase of the Morris water maze test, the latencies of the injection groups were significantly delayed, but recovered within 1 week. In the probe test, 2 of 4 indices (time in the platform zone and the number of crossings) were significantly different in the 8-μl injection group. Immunohistochemistry revealed the extent of cholinergic destruction. Activity-regulated cytoskeleton-associated protein and glutamate decarboxylase expression significantly decreased in the frontal cortex (8- and 10-μl groups), but not in the hippocampus.

CONCLUSION:

Spatial memory impairment was associated with cholinergic basal forebrain injury as well as frontocortical GABAergic hypofunction and synaptic plasticity deceleration.

• Authors: Da Un Jeong, Won Seok Chang, Yong Sup Hwang, Dongkyu Lee, Jin Woo Chang
• Journal: Dementia and geriatric cognitive disorders (Dement Geriatr Cogn Disord) Vol. 32 Issue 1 Pg. 70-8 ( 2011) ISSN: 1421-9824 [Electronic] Switzerland
• PMID: 21876356 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: 2011 S. Karger AG, Basel.

Chemical References

• 192 IgG-saporin
• Antibodies, Monoclonal
• Cholinergic Agents
• Cytoskeletal Proteins
• Nerve Tissue Proteins
• Parvalbumins
• Ribosome Inactivating Proteins, Type 1
• activity regulated cytoskeletal-associated protein
• gamma-Aminobutyric Acid
• Choline O-Acetyltransferase
• Acetylcholinesterase
• Saporins
• Glutamate Decarboxylase

Topics

• Acetylcholinesterase (metabolism)
• Animals
• Antibodies, Monoclonal (administration & dosage, pharmacology)
• Blotting, Western
• Choline O-Acetyltransferase (metabolism)
• Cholinergic Agents (administration & dosage, pharmacology)
• Cytoskeletal Proteins (biosynthesis)
• Dementia (chemically induced, psychology)
• Disease Models, Animal
• Frontal Lobe (drug effects, metabolism)
• Glutamate Decarboxylase (metabolism)
• Hippocampus (drug effects, metabolism)
• Immunohistochemistry
• Injections, Intraventricular
• Male
• Maze Learning (drug effects)
• Nerve Tissue Proteins (biosynthesis)
• Neuronal Plasticity (drug effects)
• Parvalbumins (metabolism)
• Prosencephalon (drug effects, metabolism)
• Rats
• Rats, Sprague-Dawley
• Ribosome Inactivating Proteins, Type 1 (administration & dosage, pharmacology)
• Saporins
• Synapses (drug effects)
• gamma-Aminobutyric Acid (physiology)