IGF-1 GENE THERAPY IN AN EARLY MODEL OF PARKINSON´S DISEASE

HERRERA M.; FALOMIR LOCKHART E; DOLCETTI FRANCO; BELLINI MJ; HEREÑÚ C.

Paris

Congreso; ISN-ESN Biennial Meeting; 2017

Backgound: Insulin-like growth factor-1 (IGF-1) is an endo­genous peptide trans­ported across the blood brain barrier that is pro­tective in several brain injury models, including in an animal model of Parkinson?s dis­ease (PD).Objectives: To determine in an experimental model of the neuro­patho­logy if IGF-1 gene therapy could: 1) impro­ve the cognitive dysfunc­tions and 2) induce changes in the neu­ronal activity of the affected brain areas.Methods: Male Wistar rats were bilaterally injected in CPu with either the neuro­toxic 6-hydroxy­dopamine (6OHDA rats), or vehicle (SHAM rats) as controls. Then they were divided in­to 6 experimental groups according to the gene therapy with adenovirus in hippo­campus: G1) SHAM (vehicle-vehicle), G2)6OHDA (neuro­toxic-vehicle), G3) SHAM-RAd-DS-Red, G4) SHAM-RAd-IGF-1, G5) 6OHDA-RAd-DS-Red, G6) 6OHDA-RAd-IGF-1. At 3 weeks post lesion with 6OHDA and injection with adenovirus the animals were tested for spatial memory with Y-maze test and for locomotor activity. At the end of the study the rats were perfused, the brains fixed and immuno­histochemistry performed for TH and IGF-1. All data were com­pared by 2-way ANOVA (p < 0.05 considered as statistically sig­nifi­cant).Results: 6OHDA causes cognitive deficits in G2 com­pare to G1 (p > 0.05) indicated by a decreased in spontaneo­us alter­nation percentage. This effect could not be attributed to decreased motor activity, because the number of arm entries was not sig­nifi­cantly changed and neither the number of cm performed after amphetamine admin­is­tration. This effect was partially reverted with IGF-1 overex­pression in G6 respected to G5 (p > 0.05). There were no sig­nifi­cant changes in G2 respect G5 and in G1 respected to G3 and G4. Pre­liminary results showed that IGF-1 gene therapy induce an in­crease in TH ex­pression in the nigrostriatal pathway.Conclusions: our results sug­gest that IGF-1 could be an important neuro­pro­tective mole­cule against neuro­degene­ration. Its effect on neu­ronal activity could explain in part the impro­vement in the cognitive symp­toms that we ob­served in this animal model of PD