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

MOREL GR; ZAPPA VILLAR MF; REGGIANI PC; LÓPEZ HANOTTE J; TRÍPODI LS

CABA

Congreso; Congreso SAN 2017; 2017

SAN

Alzheimer'sdisease (AD) is the most prevalent neurodegenerative pathology with noefficient therapy. Our objective is to develop biotechnological therapeuticstrategies for preventing and/or overcoming the degenerative changes in thebrain with experimental AD. In this context, we implemented gene therapy forIGF1, a potent neuroprotective molecule, in a rat model of AD. We evaluated theeffectiveness of IGF1 gene transfer to reverse or at least attenuate thedeleterious effects caused by the intracerebroventricular (icv) injection ofstreptozotocin (STZ) in rats, an experimental model of sporadic AD. Animalswere divided into three experimental groups: Sham, STZ and STZ+IGF1. STZ andSTZ+IGF1 groups received 3 mg/kg STZ-icv and, 7 days later, the STZ+IGF1 groupreceived an adenovirus vector-expressing IGF1 icv. During the last two weeksuntil the end of the study (day 24 post-STZ-icv) we performed differentbehavioral tests. STZ treated rats were deficient in all tests. Interestingly,STZ+IGF1 group improved their hippocampus-dependent learning and spatial memoryperformance in the Barnes Maze. Anxiety-like and depression-like behaviour werealso attenuated in the Marble Burying and Forced Swimming test, respectively,by exposure to IGF1. In this study, we concluded that GT for IGF1 protectedagainst behavioral impairment in our AD rat model. Thus, brain over-expressionof IGF1 emerge as promising therapeutic tool for the treatment of the AD.