Restorative effect of insulin-like growth factor-I gene therapy in the hypothalamus of senile rats with dopaminergic dysfunction.
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 x 10(9) plaque-forming units of RAd-betagal (a control adenoviral vector expressing beta-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.
Hereñú
C B
CB
INIBIOLP-Histology B, School of Medicine, UNLP, La Plata, Argentina.
Cristina
C
C
Rimoldi
O J
OJ
Becú-Villalobos
D
D
Cambiaggi
V
V
Portiansky
E L
EL
Goya
R G
RG
D000256:Adenoviridae / Q000235:genetics; D000375:Aging / Q000378:metabolism*; D000818:Animals; D002452:Cell Count; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage; D007031:Hypothalamus / Q000166:cytology / Q000378:metabolism*; D007267:Injections; D007334:Insulin-Like Growth Factor I / Q000235:genetics*; D051379:Mice; D009474:Neurons / Q000166:cytology; D011388:Prolactin / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D014161:Transduction, Genetic / Q000379:methods
D007334:Insulin-Like Growth Factor I; D011388:Prolactin; D004298:Dopamine