title: TrkA activation is sufficient to rescue axotomized cholinergic neurons.
abstract: To test the molecular nature of the NGF receptor responsible for the ability of NGF to rescue septal cholinergic neurons following axotomy, we infused polyclonal antibodies that act as specific agonists of trkA (RTA) into the lateral ventricle of fimbria-fornix lesioned animals. Rats receiving chronic intraventricular infusions of RTA showed significantly more low affinity NGF receptor immunoreactive (p75NGFR-IR) neurons on the lesioned side than did control animals 2 weeks following unilateral fimbria-fornix lesion. RTA also initiated cholinergic sprouting. Infusions of RTA in combination with an antibody that blocks p75NGFR (REX) did not reduce the cell savings effect observed with RTA alone. However, animals infused with RTA plus REX demonstrated significantly less sprouting. These findings suggest that antibody-induced trkA activation is sufficient to mediate NGF-promoted survival of axotomized cholinergic neurons in vivo.
authors.affiliation: Salk Institute for Biological Studies, La Jolla, California 92037-1099, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Lucidi-Phillipi
authors.forename: D O
authors.initials: DO
authors.lastname: Clary
authors.forename: L F
authors.initials: LF
authors.lastname: Reichardt
authors.forename: F H
authors.initials: FH
authors.lastname: Gage
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D002452:Cell Count; D002470:Cell Survival; D002799:Cholinergic Fibers / Q000502:physiology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000737:chemistry* / Q000502:physiology*; D005260:Female; D051381:Rats; D011916:Rats, Inbred F344; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism
chemical_list: D017475:Receptors, Nerve Growth Factor; D017868:Cyclic AMP-Dependent Protein Kinases