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; FALOMIR-LOCKHART, EUGENIA; DOLCETTI, FRANCO JUAN CRUZ; JÁVEGA COMETTO, MATÍAS; CERVELLINI, SOFÍA; BELLINI , MARÍA J; HEREÑÚ, CLAUDIA BEATRIZ

virtual

Encuentro; XXXVI Reunión SAN; 2021

Sociedad Argentina de Neurociencias

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 the 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.