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.

Identifying the appropriate time for deep brain stimulation to achieve spatial memory improvement on the Morris water maze

“…Moreover, Acetylcholine depresses GABAergic interneurons in the hippocampus [25]. The memory impaired rat model in this experiment was induced by selectively damaging cholinergic neurons in the basal forebrain (including MS and nucleus basalis Meynert), and hippocampus [26]. Therefore, neuronal activity in the hippocampus could be suppressed by the intact GABAergic and damaged cholinergic systems.…”

Improvements in Memory after Medial Septum Stimulation Are Associated with Changes in Hippocampal Cholinergic Activity and Neurogenesis

“…Two weeks after surgery, rats were trained in the Morris water maze as previously described [15]. Training consisted of four trials per day for 5 days with the platform in a fixed position.…”

“…The protein samples were stored at −70°C. The enzymatic activity of AChE was determined using the method of Ellman et al [36] with some modifications as previously described [15]. Briefly, 20  μ L triplicate samples were mixed with the reaction mixture (0.2 mM dithiobisnitrobenzoic acid (Sigma, St. Louis, MO), 0.56 mM acetylthiocholine iodide (Sigma, St. Louis, MO), 10  μ M tetraisopropyl pyrophosphoramide (Sigma, St. Louis, MO), and 39 mM phosphate buffer, pH 7.2) at 37°C.…”

“…We made the experiment with a rat model of dementia by intracerebroventricular (ICV) 192 IgG-saporin injections. And we found that spatial memory is profoundly impaired in this model [15]. Here, we used the 192 IgG-saporin rat model of dementia to confirm the effects of DBS on spatial memory function.…”

Activation of brain‐derived neurotrophic factor signaling in the basal forebrain reverses acute sleep deprivation‐induced fear memory impairments

“…Furthermore, the activation of cholinergic neurons can enhance arousal, attention, and memory (Eggermann, Kremer, Crochet, & Petersen, 2014; Everitt & Robbins, 1997; Fu et al, 2014; Jones, 1993; Sarter, Hasselmo, Bruno, & Givens, 2005). Impairment of spatial memory was found to be related to injury of cholinergic neurons and hypofunction of GABAergic neurons in the basal forebrain (Jeong, Chang, Hwang, Lee, & Chang, 2011). The glutamatergic and GABAergic neurons were also found to regulate the transition of cortical activity and sleep–wake states (Fuller, Sherman, Pedersen, Saper, & Lu, 2011; Kroeger et al, 2017).…”