INIBIOLP   05426
INSTITUTO DE INVESTIGACIONES BIOQUIMICAS DE LA PLATA "PROF. DR. RODOLFO R. BRENNER"
Unidad Ejecutora - UE
artículos
Título:
Gene therapy in the neuroendocrine system .
Autor/es:
HEREÑÚ CB,; MOREL GR,; BELLINI MJ,; REGGIANI PC,; SOSA YE, ;; BROWN OA,; GOYA RG
Revista:
FRONTIERS OF HORMONE RESEARCH.
Editorial:
Karger
Referencias:
Año: 2006 vol. 35 p. 135 - 142
ISSN:
0301-3073
Resumen:
ABSTRACT The implementation of experimental gene therapy in animal models of neurological diseases is an area of growing interest. Although the neuroendocrine system offers unique advantages for the assessment of in vivo gene therapy, little work has been done in this model. Here we review the core of documented studies in which in vivo gene therapy has been implemented in the neuroendocrine system of rodent models. In the hypothalamus, restorative gene therapy has been successfully implemented in Brattleboro rats, an arginine vasopressin (AVP) mutant which suffers from diabetes insipidus, in Koletsky (fak/fak) and in Zucker (fa/fa) rats which have leptin receptor mutations that render them obese, hyperphagic and hyperinsulinemic. In the above models, viral vectors expressing AVP, leptin receptor b and proopiomeolanocortin, respectively were stereotaxically injected in the relevant hypothalamic regions. In rats, aging brings about a progressive degeneration and loss of hypothalamic tuberoinfundibular dopaminergic neurons, which are involved in the tonic inhibitory control of prolactin secretion and lactotrophic cell proliferation. Stereotaxic injection of an adenoviral vector expressing insulin- like growth factor I was able to correct their chronic hyperprolactinemia and restore TIDA neuron numbers. Spontaneous intermediate lobe pituitary tumors in a retinoblastoma (Rb) tumor suppressor gene mutant mouse were corrected by injection of an adenoviral vector expressing the human Rb cDNA and experimental prolactinomas in rats were partially reduced by intrapituitary injection of an adenoviral vector expressing the HSV1-thymidine kinase suicide gene. These results suggest that further implementation of gene therapy strategies in neuroendocrine models may be highly rewarding.