INITIAL APPROACHES WITH IGF-1 GENE THERAPY IN AN ANIMAL MODEL OF PARKINSONISM ASSOCIATED TO EARLY COGNITIVE IMPAIRMENTS

HERRERA, MACARENA LORENA; FALOMIR-LOCKHART, EUGENIA; DOLCETTI, FRANCO JUAN CRUZ; CALFA, GASTON DIEGO; MOLINA, VICTOR ALEJANDRO; BELLINI, MARIA JOSE; HEREÑU, CLAUDIA B.

Torino

Encuentro; AAT-AD/PD Focus Meeting 2018; 2018

AimsParkinson´s disease (PD) is a neurodegenerative disorder with a progressive dopaminergic (DA) neuronal loss and a variety of non-motor symptoms such as cognitive dysfunctions. Growth factors as IGF-1 could be neuroprotective in PD models by improve changes in neuronal activity. The aim of this study was: 1) To determine the early cognitive decline and the correlation of hippocampal changes in 6OHDA model 2) to carry out therapeutic approaches with IGF-1 to understand plasticity processes associated with cognitive declineMethodMale Wistar rats were CPu bilaterally injected with 6OHDA or vehicle (SHAM). Independent groups were tested after 20 days post lesion for Y-maze and locomotor activity. Another set of rats were divided into 6 groups according the adenoviral therapy in hippocampus: SHAM, 6OHDA, SHAM-RAd-DS-Red, SHAM-RAd-IGF-1, 6OHDA-RAd-DS-Red and 6OHDA-RAd-IGF-1. At 20 days post lesion, were tested for behavioral tasks. Then rats were perfused, the brains fixed and IHQ performed for TH and IGF-1R and hippocampal synaptic plasticityResultsAt 20 post-lesion, early cognitive impairments and changes in the morphology of dendritic spines were observed in 6OHDA rats compared to SHAM rats. This behavioral cognitive decline was partially modified with IGF-1 overexpression in 6OHDA-RAd-IGF-1 rats. 6-OHDA was sufficient to cause memory impairments without motor deficits.ConclusionKnowledge of this neurodegenerative progression could result in potential therapeutic strategies as IGF-1 gene therapy which motivates us to further studies under this experimental model.