Profile of acetylcholinesterase in brain areas of male and female rats of adult and old age

Inhibition of acetylcholinesterase (AChE)-metabolizing enzyme of acetylchol ine, is presently the most important therapeutic target for development of cognitive enhancers. However, AChE activity in brain has not been properly evaluated on the basis of age and sex. In the present study, AChE activity was investigated in different brain areas in male and female Sprague-Dawley rats of adult (3 months) and old (18-22 months) age. AChE was assayed spec trophotometrically by modified Ellman's method. Specific activity (mu moles /min/mg of protein) of AChE was assayed in salt soluble (SS) and detergent soluble (DS) fractions of various brain areas, which consists of predominan tly G1 and G4 molecular isoforms of AChE respectively. The old male rats sh owed a decrease (40-55%) in AChE activity in frontal cortex, striatum, hypo thalamus and pens in DS fraction and there was no change in SS fraction in comparison to adult rats. In the old female rats the activity was decreased (25-40%) in frontal cortex, cerebral cortex, striatum, thalamus, cerebellu m and medulla in DS fraction whereas in SS fraction the activity was decrea sed only in hypothalamus as compared to adult. On comparing with old male r ats, old female rats showed increase in AChE activity in cerebral cortex, h ippocampus and hypothalamus of DS fraction and decrease in hypothalamus of SS fraction. There was a significant increase in AChE activity in DS fracti on of cerebral cortex, hippocampus, hypothalamus, thalamus and cerebellum i n female as compared to male adult rats. However, no significant change in AChE activity was found in the SS fraction, except hypothalamus between the se groups. Thus it appears that age alters AChE activity in different brain regions predominantly in DS fraction (G4 isoform) that may vary in male an d female. These observations have significant relevance to age related cogn itive deficits and its pharmacotherapy. (C) 2001 Elsevier Science Inc. All rights reserved.