Acetyl- l-carnitine treatment increases choline acetyltransferase activity and NGF levels in the CNS of adult rats following total fimbria-fornix transection

Abstract

Transection of the fimbria-fornix in adult rats is a useful model for producing impairments of cholinergic activity in the hippocampus (HIPP) and atrophy of the medial septum cholinergic perikarya, similar to those observed during senescence, that are possibly due to the lack of nerve growth factor (NGF) retrogradely transported from the hippocampus. In our investigation we used choline acetyltransferase (ChAT) as an index of cholinergic activity in HIPP, frontal cortex (FCX), septum and nucleus basalis magnocellularis (NBM) along with measurements of NGF levels in the HIPP. Three-month-old rats with unilateral total fimbria transection received acetyl- l-carnitine (ALCAR) (150 mg/kg/day in drinking water for 1 week before and 4 weeks after the lesion). ALCAR is a substance known to ameliorate some morphological and functional disturbances in the aging central nervous system (CNS). ChAT activity in septum and FCX, and NGF levels in HIPP were significantly increased in the treated group, compared with untreated control groups, while no changes were found in the NBM. On the other hand, a similar ALCAR treatment in unoperated animals induced an increase in ChAT activity in FCX but not in septum nor in NBM. These data are suggestive of a neurotrophic property of ALCAR exerted on those central cholinergic pathways typically damaged by aging.