This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Vasquez, E. C. Articles by Johnson, A. K. Search for Related Content PubMed PubMed Citation Articles by Vasquez, E. C. Articles by Johnson, A. K.

(Hypertension. 1999;34:756-761.)
© 1999 American Heart Association, Inc.

Scientific Contributions

Adenovirus-Mediated Gene Delivery to Hypothalamic Magnocellular Neurons in Mice

Elisardo C. Vasquez; Terry G. Beltz; Silvana S. Meyrelles; Alan Kim Johnson

From the Departments of Psychology, Pharmacology, and Medicine, and the Cardiovascular Center (T.G.B., A.K.J.), University of Iowa, Iowa City; and the Department of Physiological Sciences (E.C.V., S.S.M.), Biomedical Center, UFES, Vitoria, ES, Brazil.

Correspondence to Alan Kim Johnson, PhD, Department of Psychology, University of Iowa, 11 Seashore Hall E, Iowa City, IA 52242-1407. E-mail alan-johnson{at}uiowa.edu

Abstract—Vasopressin 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 ß-galactosidase (ß-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 2x10⁷ 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 ß-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 (4x10⁶ plaque-forming units). In material from these animals, we were able to visualize the expression of the ß-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–ß-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.

Key Words: mice • vasopressin • hypothalamus • fluorescence • gene transfer

This article has been cited by other articles:

				N. Loewen, M. P. Fautsch, W.-L. Teo, C. K. Bahler, D. H. Johnson, and E. M. Poeschla Long-Term, Targeted Genetic Modification of the Aqueous Humor Outflow Tract Coupled with Noninvasive Imaging of Gene Expression In Vivo Invest. Ophthalmol. Vis. Sci., September 1, 2004; 45(9): 3091 - 3098. [Abstract] [Full Text] [PDF]

				P. Sinnayah, T. E. Lindley, P. D. Staber, B. L. Davidson, M. D. Cassell, and R. L. Davisson Targeted viral delivery of Cre recombinase induces conditional gene deletion in cardiovascular circuits of the mouse brain Physiol Genomics, June 17, 2004; 18(1): 25 - 32. [Abstract] [Full Text] [PDF]

				L. Barzon, M. Boscaro, and G. Palu Endocrine Aspects of Cancer Gene Therapy Endocr. Rev., February 1, 2004; 25(1): 1 - 44. [Abstract] [Full Text] [PDF]

				R. L. Davisson Physiological genomic analysis of the brain renin-angiotensin system Am J Physiol Regulatory Integrative Comp Physiol, September 1, 2003; 285(3): R498 - R511. [Abstract] [Full Text] [PDF]

				P. Sinnayah, T. E. Lindley, P. D. Staber, M. D. Cassell, B. L. Davidson, and R. L. Davisson Selective Gene Transfer to Key Cardiovascular Regions of the Brain: Comparison of Two Viral Vector Systems Hypertension, February 1, 2002; 39(2): 603 - 608. [Abstract] [Full Text] [PDF]

				U. B. Kaiser Editorial: Pituitary Gene Therapy--Hypotheses on the Hypophysis Endocrinology, February 1, 2001; 142(2): 528 - 531. [Full Text] [PDF]