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Antyborzec, I.* ; O'Leary, V.B. ; Dolly, J.O.* ; Ovsepian, S.V.

Low-affinity neurotrophin receptor p75 promotes the transduction of targeted lentiviral vectors to cholinergic neurons of rat basal forebrain.

Neurotherapeutics 13, 859-870 (2016)
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Basal forebrain cholinergic neurons (BFCNs) are one of the most affected neuronal types in Alzheimer's disease (AD), with their extensive loss documented at late stages of the pathology. While discriminatory provision of neuroprotective agents and trophic factors to these cells is thought to be of substantial therapeutic potential, the intricate topography and structure of the forebrain cholinergic system imposes a major challenge. To overcome this, we took advantage of the physiological enrichment of BFCNs with a low-affinity p75 neurotrophin receptor (p75(NTR)) for their targeting by lentiviral vectors within the intact brain of adult rat. Herein, a method is described that affords selective and effective transduction of BFCNs with a green fluorescence protein (GFP) reporter, which combines streptavidin-biotin technology with anti-p75(NTR) antibody-coated lentiviral vectors. Specific GFP expression in cholinergic neurons was attained in the medial septum and nuclei of the diagonal band Broca after a single intraventricular administration of such targeted vectors. Bioelectrical activity of GFP-labeled neurons was proven to be unchanged. Thus, proof of principle is obtained for the utility of the low-affinity p75(NTR) for targeted transduction of vectors to BFCNs in vivo.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Alzheimer’s Disease ; Basal Forebrain Cholinergic Neurons ; Gene Therapy ; Neuroprotection ; Streptavidin–biotin ; P75 Neurotrophin Receptor; Nerve Growth-factor; Factor Gene-therapy; Alzheimers-disease; In-vivo; Neurodegenerative Diseases; Retrograde Transport; Septohippocampal Gaba; Discharge Properties; Nucleus Basalis; Selective Loss
ISSN (print) / ISBN 1933-7213
e-ISSN 1878-7479
Journal Neurotherapeutics
Quellenangaben Volume: 13, Issue: 4, Pages: 859-870 Article Number: , Supplement: ,
Publisher Springer
Publishing Place New York, NY
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Biological and Medical Imaging (IBMI)
Institute of Radiation Biology (ISB)