NDLI: Low-Affinity Neurotrophin Receptor p75 Promotes the Transduction of Targeted Lentiviral Vectors to Cholinergic Neurons of Rat Basal Forebrain

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Low-Affinity Neurotrophin Receptor p75 Promotes the Transduction of Targeted Lentiviral Vectors to Cholinergic Neurons of Rat Basal Forebrain

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Low-Affinity Neurotrophin Receptor p75 Promotes the Transduction of Targeted Lentiviral Vectors to Cholinergic Neurons of Rat Basal Forebrain

Content Provider	Springer Nature Link
Author	Antyborzec, Inga O’Leary, Valerie B. Dolly, James O. Ovsepian, Saak V.
Copyright Year	2016
Abstract	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.
Starting Page	859
Ending Page	870
Page Count	12
File Format	PDF
ISSN	19337213
Journal	NeuroRX
Volume Number	13
Issue Number	4
e-ISSN	18787479
Language	English
Publisher	Springer US
Publisher Date	2016-05-24
Publisher Institution	American Society for Experimental NeuroTherapeutics
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Alzheimer’s disease Basal forebrain cholinergic neurons p75 neurotrophin receptor Gene therapy Streptavidin–biotin Neuroprotection Neurosciences Neurology Neurosurgery Neurobiology
Content Type	Text
Resource Type	Article
Subject	Neurology (clinical) Pharmacology Pharmacology (medical)

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