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Adenovirus-mediated gene delivery to hypothalamic magnocellular neurons in miceVasopressin is synthesized by magnocellular neurons in supraoptic (SON) and paraventricular (PVN) hypothalamic nuclei and released by their axon terminals in the neurohypophysis (NH). With its actions as an antidiuretic hormone and vasoactive agent, vasopressin plays a pivotal role in the control of body fluids and cardiovascular homeostasis. Because of its well-defined neurobiology and functional importance, the SON/PVN-NH system is ideal to establish methods for gene transfer of genetic material into specific pathways in the mouse central nervous system. In these studies, we compared the efficiency of transferring the gene lacZ, encoding for beta-galactosidase (beta-gal), versus a gene encoding for green fluorescent protein by using replication-deficient adenovirus (Ad) vectors in adult mice. Transfection with viral concentrations up to 2 x 10(7) plaque-forming units per coverslip of NH, PVN, and SON in dissociated, cultured cells caused efficient transfection without cytotoxicity. However, over an extended period of time, higher levels (50% to 75% of the cells) of beta-gal expression were detected in comparison with green fluorescent protein (5% to 50% of the cells). With the use of a stereotaxic approach, the pituitary glands of mice were injected with Ad (4 x 10(6) plaque-forming units). In material from these animals, we were able to visualize the expression of the beta-gal gene in the NH and in magnocellular neurons of both the PVN and SON. The results of these experiments indicate that Ad-Rous sarcoma virus promoter-beta-gal is taken up by nerve terminals at the injection site (NH) and retrogradely transported to the soma of the neurons projecting to the NH. We conclude that the application of these experimental approaches will provide powerful tools for physiological studies and potential approaches to deliver therapeutic genes to treat diseases.
Document ID
20040141795
Acquisition Source
Legacy CDMS
Document Type
Reprint (Version printed in journal)
Authors
Vasquez, E. C.
(Biomedical Center UFES, Vitoria, ES, Brazil)
Beltz, T. G.
Meyrelles, S. S.
Johnson, A. K.
Date Acquired
August 22, 2013
Publication Date
October 1, 1999
Publication Information
Publication: Hypertension
Volume: 34
Issue: 4 Pt 2
ISSN: 0194-911X
Subject Category
Life Sciences (General)
Funding Number(s)
CONTRACT_GRANT: HL57472
CONTRACT_GRANT: HL14388
CONTRACT_GRANT: DK54759
Distribution Limits
Public
Copyright
Other
Keywords
Non-NASA Center
NASA Discipline Regulatory Physiology

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