title: Polyethylenimine-mediated NGF gene delivery protects transected septal cholinergic neurons.
abstract: Polyethylenimine (PEI) is an effective vehicle for in vivo gene delivery in many tissues including brain. PEI mediates transgene expression in brain neurons and glia. To investigate whether PEI-mediated nerve growth factor (NGF) gene transfer protected axotomized septal cholinergic neurons, we injected linear PEI (in vivo jetPEI, Qbiogene) complexed with a plasmid encoding for mouse NGF (PEI/pNGF-W) into the rat septum. PEI complexed with a plasmid encoding for green fluorescent protein (PEI/pGFP) was used as the control. PEI-mediated gene expression was predominantly neuronal. Fimbria-fornix transections (FFTs), conducted 1 day after rats were injected with control vector, resulted in a 70% loss of septal cholinergic neurons. In contrast, PEI/pNGF-W injection prior to FFTs attenuated the loss of septal cholinergic neurons. This is the first study, to our knowledge, that shows the neuroprotective effects induced by PEI-mediated trophic factor gene transfer in brain.
authors.affiliation: Department of Pharmacology and Therapeutics, ARB5-148, 1600 SW Archer Rd, Gainesville, FL 32610, USA. kewu@ulf.edu
authors.forename: Ke
authors.initials: K
authors.lastname: Wu
authors.forename: Craig A
authors.initials: CA
authors.lastname: Meyers
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Bennett
authors.forename: Michael A
authors.initials: MA
authors.lastname: King
authors.forename: Edwin M
authors.initials: EM
authors.lastname: Meyer
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Hughes
mesh_terms: D000818:Animals; D019771:Axotomy; D018014:Gene Transfer Techniques; D049452:Green Fluorescent Proteins; D007150:Immunohistochemistry; D007202:Indicators and Reagents; D008164:Luminescent Proteins; D051379:Mice; D020932:Nerve Growth Factor / Q000235:genetics*; D009474:Neurons / Q000473:pathology*; D010275:Parasympathetic Nervous System / Q000166:cytology / Q000473:pathology*; D011094:Polyethyleneimine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020665:Septum of Brain / Q000166:cytology / Q000473:pathology*; D013238:Stereotaxic Techniques; D019076:Transgenes
chemical_list: D007202:Indicators and Reagents; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins; D011094:Polyethyleneimine; D020932:Nerve Growth Factor