Ameliorative effects of acetyl- l-carnitine and acidic fibroblast growth factor fragment analog on brain lipid hydroperoxide level, passive avoidance learning and/or immunoreactivity for choline acetyltransferase in the medial septum in senescence-accelerated mice

Abstract

In the present study, on senescence-accelerated mice (SAM) of various ages, we examined the level of lipid hydroperoxides in the brain tissue, and the effects of acetyl- l-carnitine (ALC) and acidic fibroblast growth factor fragment analog, [Ala 16]aFGF(1–29), on the brain lipid hydroperoxide level, passive avoidance performance and/or immunoreactivity for choline acetyltransferase (ChAT) in the medial septum (MS). The brain level of lipid hydroperoxides did not show an age-dependent change in either SAMP8 or SAMR1 (control mice for SAMP8), but it was significantly higher for SAMP8 than for SAMR1 at 3, 6 and 9 months of age. Chronic administration of ALC (400 mg/kg) significantly ameliorated the deficit in learning and memory seen in saline-treated SAMP8, and also normalized the increased brain lipid hydroperoxide level in these mice. Chronic administration of [Ala 16]aFGF(1–29) (150 μg/kg) to SAMP8 also improved the learning and memory deficits and normalized the decreased ChAT activity in the cholinergic neurons of the MS in these mice. These results suggest that ALC and aFGF fragment analog can each ameliorate the cognitive disability seen in untreated SAMP8 (through a decrease in the brain lipid hydroperoxide level and through a restoration of ChAT activity in cholinergic neurons in the MS, respectively).