Increased Perivascular Norepinephrine Following Intracerebroventricular Infusion of NGF into Adult Rats

Abstract

In the present study, we used high performance liquid chromatography coupled with electrochemical detection to examine perivascular catecholamines associated with the intradural segment of the internal carotid artery following a 2-weekin vivointracerebroventricular infusion of the neurotrophin nerve growth factor (NGF). Following administration of NGF, a significant increase (87.3%) in perivascular norepinephrine (NE; μg/g) was observed when compared with vehicle-infused controls, suggesting that increased sympathetic neurotransmitter accompanies the NGF-induced sprouting response by sympathetic perivascular axons previously observed using electron microscopy (13, 15). The biochemical quantification of perivascular NE in the present study taken together with our previous morphological quantification of perivascular sprouts at the ultrastructural level reveal that the increase in NE is not proportional to the increase in the number of axons. Thus, when compared with controls, the relative amount of norepinephrine per axon apparently is reduced following NGF infusion. The apparent decrease in NE per axon following NGF infusion suggests that, during the 2-week infusion period, exogenous NGF did not stimulate the biosynthesis of perivascular NE beyond that necessary to accommodate the newly sprouted axons. These results extend our morphological findings and provide evidence for plasticity of neurotransmitter expression by adult sympathetic perivascular axonsin vivo.In addition, we provide evidence that the increased perivascular catecholamine histofluorescence previously observed following NGF infusion results from an increase in the number of perivascular axons associated with the vessel rather than from an increase in the amount of NE within individual axons.