Journal article
Adenovirus-Mediated Gene Delivery to Hypothalamic Magnocellular Neurons in Mice
Hypertension (Dallas, Tex. 1979), Vol.34(4), pp.756-761
10/1999
DOI: 10.1161/01.HYP.34.4.756
PMID: 10523356
Abstract
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 β - galactosidase (β-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 2×10 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 β - 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 (4×10 6 plaque-forming units). In material from these animals, we were able to visualize the expression of the β - 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–β - 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.
Details
- Title: Subtitle
- Adenovirus-Mediated Gene Delivery to Hypothalamic Magnocellular Neurons in Mice
- Creators
- Elisardo C Vasquez - 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, BrazilTerry G Beltz - 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, BrazilSilvana S Meyrelles - 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, BrazilAlan 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
- Resource Type
- Journal article
- Publication Details
- Hypertension (Dallas, Tex. 1979), Vol.34(4), pp.756-761
- DOI
- 10.1161/01.HYP.34.4.756
- PMID
- 10523356
- NLM abbreviation
- Hypertension
- ISSN
- 0194-911X
- eISSN
- 1524-4563
- Language
- English
- Date published
- 10/1999
- Academic Unit
- Psychological and Brain Sciences; Neuroscience and Pharmacology; Health, Sport, and Human Physiology
- Record Identifier
- 9984213407602771
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