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

HERRERA, MACARENA LORENA; CHAMPARINI, LEANDRO GABRIEL; HEREÑÚ, CLAUDIA BEATRIZ; JÁVEGA COMETTO, MATÍAS

Congreso; XXXVI Congreso anual de la Sociedad Argentina de Investigación en Neurociencias; 2021

Sociedad Argentina de Neurociencias

Parkinson´s disease is a neurodegenerative disorder with a progressive dopaminergic (DA) neuronal loss and avariety 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 thecorrelation 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. MaleWistar 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 forbehavioral tasks of cognitive performance and locomotor activity induced by amphetamine. Then rats wereperfused, the brains fixed and IHC performed for TH and Iba-1 and GFAP for glial cells. Results: At 20 days postlesion, memory deficits were observed in 6OHDA rats compared to SHAM rats. This cognitive decline waspartially modified with IGF1 gene therapy. We observed changes in GFAP+ astrocytes in different dorsalhippocampus areas, mainly in the group with IGF-1 and changes of TH expression. IGF-1 gene therapy restoredmemory impairments and modified cellular activity. Knowledge of this potential therapeutic strategy withIGF-1 gene therapy motivates us to further studies under this experimental model