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 ameliorate age-related neurodegeneration, but it cannot cross the blood-brain barrier (BBB). NGF conjugated to an antibody against the transferrin receptor (OX-26) crosses the BBB and affects the biochemistry and morphology of NGF-deprived basal forebrain neurons. The rapid actions of NGF, including electrophysiological effects on these neurons, are not well understood. In the present study, two model systems in which basal forebrain neurons either respond dysfunctionally to NGF (aged rats) or do not have access to target-derived NGF (intraocular transplants of forebrain neurons) were tested. One group of transplanted and one group of aged animals received unconjugated OX-26 and NGF comixture as a control, while other groups received replacement NGF in the form of OX-26-NGF conjugate during the 3 months preceding the electrophysiological recording session. Neurons from animals in both the transplanted 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, forebrain transplants and aged brains were immunocytochemically stained for the low-affinity NGF receptor. All conjugate treatment groups showed significantly greater staining intensity compared to controls. These data from both transplants and aged rats in situ indicate that NGF-deprived basal forebrain neurons respond to acute NGF with an increased firing rate. This novel finding may have importance even for long-term biological effects of this trophic factor in the basal forebrain.
Albeck
D S
DS
Department of Basic Science, University of Colorado Health Sciences Center, Denver, 80262, USA. David.Albeck@UCHSC.edu
Bäckman
C
C
Veng
L
L
Friden
P
P
Rose
G M
GM
Granholm
A
A
D000375:Aging / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D005260:Female; D016332:Fetal Tissue Transplantation; D006801:Humans; D009414:Nerve Growth Factors / Q000378:metabolism / Q000494:pharmacology*; D016501:Neurites / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology*; D009799:Ocular Physiological Phenomena; D016548:Prosencephalon / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D011916:Rats, Inbred F344; D012688:Septum Pellucidum / Q000187:drug effects / Q000196:embryology; D013997:Time Factors
D009414:Nerve Growth Factors