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Restorative effect of insulin-like growth factor-I gene therapy in the hypothalamus of senile rats with dopaminergic dysfunction

Gene Therapy volume 14, pages 237–245 (2007)Cite this article

Abstract

Insulin-like growth factor-I (IGF-I) is emerging as a powerful neuroprotective molecule that is strongly induced in the central nervous system after different insults. We constructed a recombinant adenoviral vector (RAd-IGFI) harboring the gene for rat IGF-I and used it to implement IGF-I gene therapy in the hypothalamus of senile female rats, which display hypothalamic dopaminergic (DA) neurodegeneration and as a consequence, chronic hyperprolactinemia. Restorative IGF-I gene therapy was implemented in young (5 months) and senile (28 months) female rats, which received a single intrahypothalamic injection of 3 × 109 plaque-forming units of RAd-βgal (a control adenoviral vector expressing β-galactosidase) or RAd-IGFI and were killed 17 days post-injection. In the young animals, neither vector modified serum prolactin levels, but in the RAd-IGFI-injected senile rats a nearly full reversion of their hyperprolactinemic status was recorded. Morphometric analysis revealed a significant increase in the total number of tyrosine hydroxylase-positive cells in the hypothalamus of experimental as compared with control senile animals (5874±486 and 3390±498, respectively). Our results indicate that IGF-I gene therapy in senile female rats is highly effective for restoring their hypothalamic DA dysfunction and thus reversing their chronic hyperprolactinemia.

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Acknowledgements

This work was supported in part by Grants # PICT13588 and PICT10663 from the (Argentine) National Agency for the Promotion of Science and Technology and Grant NIH#1 R21 TW006665 from the Fogarty International Center and the National Institute on Aging (USA) to RGG, and Grant # PICT 12544 to ELP. We thank Ms Yolanda Sosa for technical assistance and Ms Paula Reggiani for graphic design assistance. OJR, DBV, ELP and RGG are Research Career scientists of the Argentine Research Council (CONICET). CBH and CC are doctoral fellowship recipients from CONICET.

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Authors and Affiliations

  1. INIBIOLP-Histology B, School of Medicine, UNLP, La Plata, Argentina

    C B Hereñú, O J Rimoldi & R G Goya

  2. IBYME-CONICET, Buenos Aires, Argentina

    C Cristina & D Becú-Villalobos

  3. Institute of Anatomy, School of Veterinary Sciences, UNLP, La Plata, Argentina

    V Cambiaggi

  4. Institute of Pathology, School of Veterinary Sciences, UNLP, La Plata, Argentina

    E L Portiansky

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  1. C B Hereñú
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  2. C Cristina
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Correspondence to R G Goya.

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Hereñú, C., Cristina, C., Rimoldi, O. et al. Restorative effect of insulin-like growth factor-I gene therapy in the hypothalamus of senile rats with dopaminergic dysfunction. Gene Ther 14, 237–245 (2007). https://doi.org/10.1038/sj.gt.3302870

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