title: AAV2/5-mediated NGF gene delivery protects septal cholinergic neurons following axotomy.
abstract: Nerve growth factor (NGF) therapy has been proposed to treat cognitive impairments in aged patients including those with Alzheimer's disease. Various viral vectors, including adeno-associated virus serotype 2 (AAV2), have been investigated for their ability to deliver NGF in brain. In this study, hybrid vectors (AAV2/5) consisting of the genome of recombinant AAV2 and the capsid of AAV serotype 5 were evaluated for their ability to deliver NGF and green fluorescent protein (GFP) genes into brain. Compared to AAV2, AAV2/5 consistently led to more septal neurons being transduced with GFP over a wider range of distribution. However, both types of vector provided similar levels of long-term (17 weeks) protection of septal cholinergic neurons from axotomy and led to similar levels of NGF accumulation in this region. These results demonstrate that rAAV-mediated NGF gene delivery is neuroprotective for an extended period of time, but that factors other than transduction efficiency appear to determine transgenic NGF expression in septum.
authors.affiliation: Department of Pharmacology and Therapeutics, University of Florida, ARB5-148, 1600 SW Archer Rd, Gainesville, FL 32610, USA. kewu@ufl.edu
authors.forename: Ke
authors.initials: K
authors.lastname: Wu
authors.forename: Edwin M
authors.initials: EM
authors.lastname: Meyer
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Bennett
authors.forename: Craig A
authors.initials: CA
authors.lastname: Meyers
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Hughes
authors.forename: Michael A
authors.initials: MA
authors.lastname: King
mesh_terms: D000818:Animals; D019771:Axotomy; D036022:Capsid Proteins / Q000235:genetics*; D002795:Choline O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D020712:Fornix, Brain / Q000502:physiology; D017930:Genes, Reporter / Q000235:genetics; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000235:genetics; D007150:Immunohistochemistry; D008297:Male; D009414:Nerve Growth Factors / Q000235:genetics*; D010275:Parasympathetic Nervous System / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020665:Septum of Brain / Q000502:physiology*; D013238:Stereotaxic Techniques
chemical_list: D036022:Capsid Proteins; D009414:Nerve Growth Factors; C018315:hexon capsid protein, Adenovirus; D049452:Green Fluorescent Proteins; D002795:Choline O-Acetyltransferase