Restorative effect of intracerebroventricular insulin-like growth factor-I gene therapy on motor performance in aging rats.
Insulin-like growth factor-I (IGF-I) is a powerful neuroprotective molecule in the brain and spinal cord. We have previously shown that intracerebroventricular (i.c.v.) IGF-I gene therapy is an effective strategy to increase IGF-I levels in the cerebrospinal fluid (CSF). Since aging in rats is associated with severe motor function deterioration, we implemented i.c.v. IGF-I gene therapy in very old rats (30-31 months) and assessed the beneficial impact on motor performance. We used recombinant adenovectors (RAds) expressing either green fluorescent protein (GFP) or rat IGF-I. Injection in the lateral or fourth ventricle led to high transgene expression in the ependymal cell layer in the brain and cervical spinal cord. RAd-IGF-I-injected rats but not RAd-GFP-injected controls, showed significantly increased levels of CSF IGF-I. Motor tests showed the expected age-related decline in aged rats. Seventeen-day IGF-I gene therapy induced a significant improvement in motor performance in the aged but not in the young animals. These results show that IGF-I is an effective restorative molecule in the aging brain and spinal cord. The data also reveal that the ependymal route constitutes a promising approach for implementing protective IGF-I gene therapy in the aging CNS.
Institute of Pathology, School of Veterinary Sciences, National University of La Plata, La Plata 1900, Argentina.
F
F
Nishida
G R
GR
Morel
C B
CB
Hereñú
J I
JI
Schwerdt
R G
RG
Goya
E L
EL
Portiansky
D000367:Age Factors; D000375:Aging / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics / Q000494:pharmacology*; D007276:Injections, Intraventricular / Q000379:methods; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000235:genetics*; D009069:Movement Disorders / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley
D007334:Insulin-Like Growth Factor I