IGF-1 gene therapy in early Parkinson´s disease

HERRERA, MACARENA LORENA; FALOMIR-LOCKHART, EUGENIA; DOLCETTI, FRANCO JUAN CRUZ; BELLINI , MARÍA J; HEREÑÚ, CLAUDIA BEATRIZ

Paris

Congreso; 2017 ISN-ESN Meeting; 2017

ISN-ESN

Backgound: Insulin-like growth factor-1 (IGF-1) is an endo¬genous peptide trans¬ported across the blood brain barrier that is pro¬tective in several brain injury models, including in an animal model of Parkinson?s dis¬ease (PD).Objectives: To determine in an experimental model of the neuro¬patho¬logy if IGF-1 gene therapy could: 1) impro¬ve the cognitive dysfunc¬tions and 2) induce changes in the neu¬ronal activity of the affected brain areas.Methods: Male Wistar rats were bilaterally injected in CPu with either the neuro¬toxic 6-hydroxy¬dopamine (6OHDA rats), or vehicle (SHAM rats) as controls. Then they were divided in¬to 6 experimental groups according to the gene therapy with adenovirus in hippo¬campus: G1) SHAM (vehicle-vehicle), G2)6OHDA (neuro-toxic-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 immuno¬histochemistry performed for TH and IGF-1. All data were com¬pared by 2-way ANOVA (p < 0.05 considered as statistically sig¬nifi¬cant).Results: 6OHDA causes cognitive deficits in G2 com-pare to G1 (p > 0.05) indicated by a decreased in spontaneo¬us alter¬nation percentage. This effect could not be attributed to decreased motor activity, because the number of arm entries was not sig¬nifi¬cantly changed and neither the number of cm performed after amphetamine admin¬is¬tration. This effect was partially reverted with IGF-1 overex¬pression in G6 respected to G5 (p > 0.05). There were no sig¬nifi¬cant changes in G2 respect G5 and in G1 respected to G3 and G4. Pre¬liminary results showed that IGF-1 gene therapy induce an in-crease in TH ex¬pression in the nigrostriatal pathway.Conclusions: our results sug¬gest that IGF-1 could be an important neuro¬pro¬tective mole¬cule against neuro¬degene¬ration. Its effect on neu¬ronal activity could explain in part the impro¬vement in the cognitive symp¬toms that we ob¬served in this animal model of PD