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.