Strain and regional dependence of alternate splicing of acetylcholinesterase in the murine brain following stress or treatment with diisopropylfluorophosphate

Abstract

Induction of the rare readthrough variant of acetylcholinesterase (AChE-R) by an acetylcholinesterase (AChE) inhibitor or by stress was tested in four mouse strains that differ in their behavioural profiles on tests of anxiety and depression. BALB/C, C57Bl/6, C3H/He and CD-1 mouse strains were tested in the elevated plus maze in two sessions, separated by 48h. All strains, except CD-1, showed the expected reduction in open arm exploration on the second session. BALB/C and C3H mice spent a greater proportion of the time in the open arms on the first exposure, but spent more time immobile in the maze compared to the CD1 and C57 strains. Immobility was attenuated upon the second exposure in all strains, except the BALB/C mice. Real-time PCR was used to investigate regional and strain differences in induction of AChE-R mRNA following four daily injections of diisopropylfluorophosphate (DFP) (.1mg/kg). AChE-R induction was found in the frontal cortex, but not in amygdala, hippocampus or striatum of CD-1 mice. Nor was there AChE-R induction in the brains of the inbred strains. Four daily sessions of swim stress were used to investigate stress-induced induction of AChE-R. BALB/C mice showed significantly more immobility in the forced swim test (FST) compared to the other strains. FST did not induce AChE-R mRNA in any brain region tested; however, AChE-R mRNA expression in the frontal cortex was negatively correlated with immobility in the FST.