Restorative effect of intracerebroventricular insulin-like growth factor-I gene therapy on motor performance in aging rats.

NISHIDA FABIAN; MOREL G; HEREÑU C; SCHWERDT J; GOYA R; PORTIANSKY E

NEUROSCIENCE

PERGAMON-ELSEVIER SCIENCE LTD

Año: 2011 vol. 17 p. 195 - 206

0306-4522

Abstract—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-GFPinjected 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. © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.