Early Cognitive Impairment associated with a parkinsonian animal model: synaptic plasticity and initial approaches with IGF-1 gene therapy

HERRERA, MACARENA LORENA; ESPEJO, PABLO; CALFA, GASTON; BELLINI , MARÍA J; MOLINA, VICTOR A; HEREÑU, CLAUDIA B.

Mar del Plata

Congreso; XXXII Congress of the Argentine Society for Research in Neuroscience; 2017

Sociedad Argentina de Neurociencias

Parkinson´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. 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 decline. Male Wistar rats were CPu bilaterally injected with 6OHDA or vehicle (SHAM). Independent groups were tested after 7, 14, 20 and 28 days 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 plasticity. At 20 post-lesion, memory deficits, changes in 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. Knowledge 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.