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PS4-05 | IGF-1 GENE THERAPY ON DOPAMINERGIC NEURONS AND GLIAL CELLS INTERACTION IN EARLY COGNITIVE DEFICITS IN RAT PARKINSONISM MODEL

Macarena Lorena Herrera

Departamento de Farmacología. Facultad de Ciencias Químicas. Universidad Nacional de Córdoba. Instituto de Farmacología Experimental de Córdoba (IFEC). CONICET

Parkinson´s disease is a neurodegenerative disorder with a progressive dopaminergic (DA) neuronal loss and a variety of non-motor symptoms, such as cognitive dysfunctions. IGF-1 neuroprotective effects could be, in part, due to changes in the activity of neurons and glia. Aims: 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 and 3) to analyze modifications on glial cells through different brain areas involved in the proposed circuit. Male Wistar rats were divided into 6 groups according to CPu bilaterally injection with 6OHDA or vehicle (SHAM) and the adenoviral therapy in hippocampus with RAd-DSRed or RAd-IGF1. At 3 weeks, rats were tested for behavioral tasks of cognitive performance and locomotor activity induced by amphetamine. Then rats were perfused, the brains fixed and IHC performed for TH and Iba-1 and GFAP for glial cells. Results: At 20 days post-lesion, memory deficits were observed in 6OHDA rats compared to SHAM rats. This cognitive decline was partially modified with IGF1 gene therapy. We observed changes in GFAP+ astrocytes in different dorsal hippocampus areas, mainly in the group with IGF-1 and changes of TH expression. IGF-1 gene therapy restored memory impairments and modified cellular activity. Knowledge of this potential therapeutic strategy with IGF-1 gene therapy motivates us to further studies under this experimental model