Insulin-like Growth Factor 1 (IGF1) gene therapy modulates behavior, neurogenesis, and synaptic proteins in a rat model of sporadic Alzheimer's disease

ZAPPA VILLAR MF; LOPEZ HANOTTE J; PARDO J; REGGIANI PC

VIRTUAL

Congreso; Alzheimer's Association International Conference 2020; 2020

Alzheimer?s Association

SporadicAlzheimer?s disease (SAD) is the most prevalent neurodegenerative disorder worldwide and it is characterized by progressivememory loss and cognitive impairment. Brain activationof insulin signaling preserves memory in animal models and appears beneficial forpatients. In contrast, the role of insulin-like growth factor 1 (IGF1) remainscontroversial. Our aim was to determine thepossible protective actions of IGF1 ina rat SAD model induced by intracerebroventricular injection of streptozotocin(icv-STZ). To this end, we drove the expression ofIGF1 using a recombinant adenoviral vector, RAd-IGF1.Method:We evaluated 3 animalgroups: Sham, STZ and STZ+IGF1. STZ and STZ+IGF1 groups were injected with 3 mg/kgicv-STZ and, 7 days later, the STZ+IGF1 group received the icv-RAd-IGF1. Duringthe last two weeks until the end of the study (day 24 post icv-STZ), weperformed several behavioral tests. Additionally, we analyzed neuroblast cells,synaptic proteins and IGF1-signaling pathway proteins in the hippocampus. Result: IGF1improved marble-burying behavior, hippocampus-dependent spatial memory, objectrecognition memory and decreased depression-like behavior, all features affectedby STZ. Also, brain IGF1 overexpression restored neurogenesis, enhanced SYT2,PSD95 and GAD65/67 levels, and modulated the IGF1 receptor signaling pathway inSTZ animals. Conclusion: Results indicate a protective role of IGF1 in our SADmodel, as itwas effective against behavior deficits andameliorated hippocampal protein alterations induced by STZ. We conclude that IGF1 therapy has an interesting potential for SADtreatment.