Exogenous Nerve Growth Factor Increases the Activity of High‐Affinity Choline Uptake and Choline Acetyltransferase in Brain of Fisher 344 Male Rats

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Abstract
The objective of this study was to determine the effect of age and chronic intracerebral administration of nerve growth factor (NGF) on the activity of the presynaptic cholinergic neuronal markers hemicholinium‐sensitive high‐affinity choline uptake (HACU) and choline acetyltransferase (ChAT) in the brain of Fisher 344 male rats, in 24‐month‐old rats, a substantial decrease in ChAT activity (30%) was measured in striatum, and decreases in HACU were found in frontal cortex (28%) and hippocampus (23%) compared with 4‐month‐old controls. Cholinergic neurons in brain of both young adult and aged rats responded to administration of exogenous NGF by increased expression of both phenotypes. In 4‐month‐old animals, NGF treatment at 1.2 μg/ day resulted in increased activities of both ChAT and HACU in striatum (175 and 170%, respectively), frontal cortex (133 and 125%), and hippocampus (137 and 125%) compared with untreated and vehicle‐treated 4‐month‐old animals; vehicle treatment had no effect on the activity of either marker. In 24‐month‐old animals treated with NGF for 2 weeks, ChAT activity was increased in striatum (179%), frontal cortex (134%), and hippocampus (119%) compared with 24‐month‐old control animals. Synaptosomal HACU in 24‐month‐old rats was increased in striatum (151%) and frontal cortex (128%) after 2 weeks of NGF treatment, but hippocampal HACU was not significantly different from control values. Treatment of 24‐month‐old rats with NGF for 4 weeks produced further increases in ChAT activity and HACU in striatum and frontal cortex; in hippocampus, the 4‐week treatment did increase HACU, but ChAT activity was not further increased over that produced by 2 weeks of NGF administration. These data indicate an age‐related differential regulation of ChAT activity and HACU between specific brain areas. In addition, NGF stimulated phenotypic expression of these cholinergic markers in both young adult and aged rat brain; there might be an age‐associated differential sensitivity of particular brain regions to exogenous NGF.