Neuroprotective potential of Insulin-like Growth Factor 1 (IGF1) in a rat model of sporadic Alzheimer's disease

TRÍPODI, LUCÍA S.; ZAPPA-VILLAR, MARÍA F.; MOREL, GUSTAVO R.; LÓPEZ HANOTTE, JULIETTE; REGGIANI, PAULA C.

Mar del Plata

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

Sociedad Argentina de Investigación en Neurociencias (SAN)

Alzheimer's disease (AD) is the most prevalent neurodegenerative pathology with no efficient therapy. Our objective is to develop biotechnological therapeutic strategies for preventing and/or overcoming the degenerative changes in the brain with experimental AD. In this context, we implemented gene therapy for Insulin-like Growth Factor 1 (IGF1), a potent neuroprotective molecule, in rats. We evaluated the effectiveness of IGF1 gene transfer to reverse or at least attenuate the deleterious effects caused by the intracerebroventricular (icv) injection of streptozotocin (STZ), an experimental model of sporadic AD. Animals were submitted into three experimental groups: Sham, STZ and STZ+IGF1. STZ and STZ+IGF1 groups received 3 mg/kg STZ-icv and, 7 days later, the STZ+IGF1 group received an adenovirus vector-expressing IGF1 icv. During the last two weeks until the end of the study (day 24 post-STZ-icv) we performed different behavioral tests. STZ treated rats were deficient in all tests. Interestingly, STZ+IGF1 group improved their hippocampus-dependent learning and spatial memory performance in the Barnes Maze. Anxiety-like and depression-like behaviour were also attenuated in the Marble Burying and Forced Swimming test, respectively, by exposure to IGF1. In this study, we concluded that brain over-expression of IGF1 protected against behavioral impairment in our AD rat model. Thus, IGF1 emerge as promising therapeutic molecule for AD treatment.