Dopaminergic neurodegeneration and neuroinflammation: modulation by IGF-I gene therapy

OTAMENDI, ANDREA; FALOMIR LOCKHART, EUGENIA; BELLINI, MARIA JOSE; BASMADJIAN, OSVALDO MARTÍN; DOLCETTI, FRANCO JUAN CRUZ; HEREÑÚ, CLAUDIA BEATRIZ; HERRERA, MACARENA LORENA; CHAMPARINI, LEANDRO; MOLINA, VA

Cordoba

Congreso; XXXIII Congress of the Argentine Society for Research in Neuroscience; 2018

Insulin-like growth factor 1 (IGF-1) is emerging as a powerful neuroprotective molecule since most brain disorders are accompanied by IGF-1 deficiency and/or resistance. IGF-1 has a wide variety of functions and its study could provide the basis to prevent the deleterious effects of neurodegeneration. The aim of this study is to explore the effects of IGF-1 gene therapy on different experimental models of neurodegeneration and neuroinflammation. Under an experimental model of Parkinson?s disease, hippocampal IGF-1 gene therapy has important effects on neuronal activity that could explain, in part, the improvement in working memory dysfunction that we observed after 20 days of neurodegeneration in rats injected with 6-OHDA. ICV IGF-1 gene therapy induced a restorative effect in the hypothalamus of senile rats with DA dysfunction, and a significant improvement in motor performance in aged rats. Besides, in a clinical assessment of frailty in female and male mice, we observed cognitive and motor improvements in the groups injected with IGF-I. Neuroinflammation comprises glial cells activation and the release of pro-inflammatory molecules, which is a normal response oriented to protect neural tissue. With regard to this, IGF-1 gene delivery to astrocytes in vitro reduces their inflammatory response to lipopolysaccharide. Besides, IGF-1 exerts neuroprotective actions in a traumatic brain injury, which triggers the activation of glial cells in the cortex. Our results provide a support to develop new therapeutic approaches