Rejuvenating Effect of Long-Term Insulin-Like Growth Factor-I Gene Therapy in the Hypothalamus of Aged Rats with Dopaminergic Dysfunction

Rejuvenation Res. 2018 Apr;21(2):102-108. doi: 10.1089/rej.2017.1935. Epub 2017 Sep 6.


The aging female rat constitutes an interesting model of spontaneous and progressive age-related dopaminergic dysfunction as it allows assessing new therapeutic strategies for Parkinson's disease. Insulin-like growth factor I (IGF-I) is emerging as a powerful neuroprotective molecule, strongly induced in the central nervous system after different insults. We constructed a helper-dependent recombinant adenoviral vector (HDRAd-IGFI) harboring the gene for rat IGF-I. This was used to implement long-term IGF-I gene therapy in the hypothalamus of aged female rats, which display hypothalamic dopaminergic (DA) dysfunction and, as a consequence, chronic hyperprolactinemia. Rejuvenating long-term IGF-I gene therapy was implemented in young (3 months) and aged (24 months) female rats, which received a single intrahypothalamic injection of 4 × 109 viral particles of either HD-RAd-IGFI or HD-RAd-DsRed (control vector) and were sacrificed 119 days postinjection. In the young animals, neither vector modified serum prolactin (PRL) levels, but in the RAd-IGFI-injected aged rats a nearly full reversion of their hyperprolactinemic status was recorded. Morphometric analysis revealed a significant increase in the total number of tyrosine hydroxylase (TH)-positive cells in the hypothalamus of experimental compared with control aged animals (5874 ± 486 and 3390 ± 498, respectively). Our results indicate that IGF-I gene therapy in aged female rats is highly effective in rejuvenating the hypothalamic DA neuron groups.

Keywords: IGF-I; TIDA neurons; aging; gene therapy; hyperprolactinemia; neurodegeneration; rejuvenation.

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Dopamine / metabolism*
  • Female
  • Genetic Therapy / methods*
  • Genetic Vectors / administration & dosage*
  • Hyperprolactinemia / genetics
  • Hyperprolactinemia / pathology
  • Hyperprolactinemia / therapy*
  • Hypothalamus / cytology
  • Hypothalamus / metabolism
  • Insulin-Like Growth Factor I / genetics*
  • Rats
  • Rats, Sprague-Dawley
  • Rejuvenation*


  • IGF1 protein, human
  • Insulin-Like Growth Factor I
  • Dopamine