Acute application of NGF increases the firing rate of aged rat basal forebrain neurons

Nerve growth factor (NGF) has been widely used in animal models to ameliora te age-related neurodegeneration, but it cannot cross the blood-brain barri er (BBB). NGF conjugated to an antibody against the transferrin receptor (O X-26) crosses the BBB and affects the biochemistry and morphology of NGF-de prived basal forebrain neurons. The rapid actions of NGF, including electro physiological effects on these neurons, are not well understood. In the pre sent study, two model systems in which basal forebrain neurons either respo nd dysfunctionally to NGF (aged rats) or do not have access to target-deriv ed NGF (intraocular transplants of forebrain neurons) were tested. One grou p of transplanted and one group of aged animals received unconjugated OX-26 and NGF comixture as a control, while other groups received replacement NG F in the form of OX-26-NGF conjugate during the 3 months preceding the elec trophysiological recording session. Neurons from animals in both the transp lanted and aged control groups showed a significant increase in firing rate in response to acute NGF application, while none of the conjugate-treated groups or young intact rats showed any response. After the recordings, fore brain transplants and aged brains were immunocytochemically stained for the low-affinity NGF receptor. All conjugate treatment groups showed significa ntly greater staining intensity compared to controls. These data from both transplants and aged rats in situ indicate that NGF-deprived basal forebrai n neurons respond to acute NGF with an increased firing rate. This novel fi nding may have importance even for long-term biological effects of this tro phic factor in the basal forebrain.