AAV2/5-mediated NGF gene delivery protects septal cholinergic neurons following axotomy.
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.
Wu
Ke
K
Department of Pharmacology and Therapeutics, University of Florida, ARB5-148, 1600 SW Archer Rd, Gainesville, FL 32610, USA. kewu@ufl.edu
Meyer
Edwin M
EM
Bennett
Jennifer A
JA
Meyers
Craig A
CA
Hughes
Jeffrey A
JA
King
Michael A
MA
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
D036022:Capsid Proteins; D009414:Nerve Growth Factors; C018315:hexon capsid protein, Adenovirus; D049452:Green Fluorescent Proteins; D002795:Choline O-Acetyltransferase