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      Distribution of Fluorescence following Injection of Recombinant Adeno-Associated Virus Encoding Green Fluorescent Protein into the Paraventricular Nucleus

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          Abstract

          We have used recombinant type 2 adeno-associated virus to deliver the gene encoding green fluorescent protein into the central nervous system of adult rats. Gene expression, determined by fluorescent microscopy, was observed not only at the site of injection but also in axons following known neuroanatomical pathways. We have demonstrated a spread of enhanced green fluorescent protein from the paraventricular nucleus of the hypothalamus into the median eminence and neurohypophysis. Cell bodies containing enhanced green fluorescent protein were also visualized in the paraventricular nucleus contralateral to the side of injection. These findings suggest that gene transfer by recombinant adeno-associated virus could be used as a tool to investigate hypothalamic-pituitary interactions and, elsewhere in the central nervous system, to trace axonal pathways.

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          Long-term gene expression and phenotypic correction using adeno-associated virus vectors in the mammalian brain.

          Adeno-associated viral (AAV) vectors are non-pathogenic, integrating DNA vectors in which all viral genes are removed and helper virus is completely eliminated. To evaluate this system in the post-mitotic cells of the brain, we found that an AAV vector containing the lacZ gene (AAVlac) resulted in expression of beta-galactosidase up to three months post-injection in vivo. A second vector expressing human tyrosine hydroxylase (AAVth) was injected into the denervated striatum of unilateral 6-hydroxydopamine-lesioned rats. Tyrosine hydroxylase (TH) immunoreactivity was detectable in striatal neurons and glia for up to four months and we also found significant behavioural recovery in lesioned rats treated with AAVth versus AAVlac controls. Safe and stable TH gene transfer into the denervated striatum may have potential for the genetic therapy of Parkinson's disease.
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            Interacting Appetite-Regulating Pathways in the Hypothalamic Regulation of Body Weight

            S P Kalra (1999)
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              Retrograde transport of horseradish peroxidase in the magnocellular neurosecretory system of the rat

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                Author and article information

                Journal
                NEN
                Neuroendocrinology
                10.1159/issn.0028-3835
                Neuroendocrinology
                S. Karger AG
                0028-3835
                1423-0194
                2003
                February 2003
                10 March 2003
                : 77
                : 2
                : 100-104
                Affiliations
                Endocrine Unit, Imperial College Faculty of Medicine, Hammersmith Campus, London, UK
                Article
                68651 Neuroendocrinology 2003;77:100–104
                10.1159/000068651
                12624531
                e36c48cd-4c56-46ee-bfee-b5e17d518880
                © 2003 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 20 August 2002
                : 19 November 2002
                Page count
                Figures: 1, Tables: 1, References: 18, Pages: 5
                Categories
                Organization and Regulation of Hypothalamic Neurons

                Endocrinology & Diabetes,Neurology,Nutrition & Dietetics,Sexual medicine,Internal medicine,Pharmacology & Pharmaceutical medicine
                Neurone mapping,Adeno-associated virus,Paraventricular nucleus,Green fluorescent protein,Median eminence

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