Methanesulfonyl fluoride, an acetylcholinesterase inhibitor, attenuates simple learning and memory deficits in ischemic rats.

Abstract

Methanesulfonyl fluoride (MSF), a highly selective CNS inhibitor of acetylcholinesterase, has been recently demonstrated to promote improvement in cognitive performance in patients with senile dementia of Alzheimer type. Because a similar cognitive impairment may accompany stroke, we investigated in the present study whether treatment with MSF could produce beneficial effects in adult rats subjected to an experimental stroke model. Sprague-Dawley rats received transient 60 min intraluminal occlusion of the right middle cerebral artery (MCAo) and were given i.p. injections of either MSF (1 mg/kg at 24 and 48 h post-MCAo and 0.3 mg/kg thereafter every other day) or the vehicle, peanut oil, for 4 weeks. Behavioral tests and biochemical assays were performed at 28 days post-surgery. MSF treatment produced about 90% inhibition of acetylcholinesterase in the brain. Ischemic animals that received the vehicle displayed significant elevated body swing biased activity (84.8 +/- 10%) and significantly prolonged acquisition (398 +/- 62 s) and shortened retention (79 +/- 26 s) of the passive avoidance task. Interestingly, while the ischemic animals that received the MSF exhibited elevated body swing biased activity (87.7 +/- 8%), they performed significantly better in the passive avoidance task (255 +/- 36 s and 145 +/- 18 s in acquisition and retention) than the vehicle-treated animals. Moreover, whereas brains from both groups of animals revealed similar extent and degree of cerebral infarction, the MSF-treated ischemic animals showed more intense immunoreactivity, as well as a significantly higher number (10-15% increase) of septal choline acetyltransferase-positive cells than the vehicle-treated ischemic animals. These results show that MSF, possibly by preserving a functional cholinergic system, attenuated stroke-induced deficits in a simple learning and memory task.

• Authors: Cesario V Borlongan, Isabel C Sumaya, Donald E Moss
• Journal: Brain research (Brain Res) Vol. 1038 Issue 1 Pg. 50-8 (Mar 15 2005) ISSN: 0006-8993 [Print] Netherlands
• PMID: 15748872 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Cholinesterase Inhibitors
• Sulfones
• methanesulfonyl fluoride
• Choline O-Acetyltransferase
• Acetylcholinesterase

Topics

• Acetylcholinesterase (drug effects)
• Animals
• Avoidance Learning (drug effects)
• Cerebral Infarction (complications, enzymology, prevention & control)
• Choline O-Acetyltransferase (drug effects)
• Cholinesterase Inhibitors (pharmacology)
• Cognition Disorders (enzymology, etiology, prevention & control)
• Disease Models, Animal
• Functional Laterality (drug effects)
• Infarction, Middle Cerebral Artery (complications, drug therapy, enzymology)
• Male
• Memory Disorders (enzymology, etiology, prevention & control)
• Motor Activity (drug effects)
• Rats
• Rats, Sprague-Dawley
• Stroke (complications, drug therapy, enzymology)
• Sulfones (pharmacology)