Neuroprotective Insulin-like Growth factor 1 (IGF1) gene therapy for a rat model of sporadic Alzheimer?s disease.

LÓPEZ HANOTTE J; ZAPPA VILLAR MF; PARDO J; CAMIHORT GA; REGGIANI PC

Congreso; XXXIV Reunión Anual SAN 2019; 2019

the Argentinian Society for Neuroscience Research (SAN)

 Sporadic Alzheimer?s disease (SAD) is a progressiveneurodegenerative disorder with no cure. We are interested in developingtherapeutic strategies to overcome SAD-neurodegeneration. To this end, weimplemented gene therapy (GT) for IGF1 in a rat SAD model induced byintracerebroventricular injection of streptozotocin (icv-STZ). Animals weredivided into 3 experimental groups: Sham, STZ and STZ+IGF1. STZ and STZ+IGF1groups received 3 mg/kg STZ-icv. Seven days later, the STZ+IGF1 group receivedicv an adenoviral vector expressing recombinant IGF1. During the last two weeksuntil the end of the study (day 24 post-icv-STZ), we performed severalbehavioral tests. Additionally, we performed in the hippocampusinmunohistochemistry to analyze neurogenesis and microglial cells, and WesternBlots to assess the levels of proteins involved in the IGF1 signaling pathway.Our results show that IGF1-GT improved marble-burying behavior,hippocampus-dependent spatial memory, object recognition memory and decreaseddepression-like behavior, all features affected by STZ. Also, brain IGF1 overexpressionrestored neurogenesis in the STZ animals and modulated the microglialpopulation. Importantly, the assessment of phosphorylated proteins levelsrevealed that IGF1 therapy effect was mediated by triggering IGF1 receptorsignaling pathway. We conclude that IGF1 over-expression has an interestingpotential for the treatment of SAD.