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

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

VIRTUAL

Conferencia; Alzheimer Association International Conference (AAIC) 2020; 2020

Alzheimer?s Association

Background: Sporadic Alzheimer?s disease (SAD) is the most prevalent neurodegenerative disorderworldwide and it is characterized by progressive memory loss and cognitive impairment. Brainactivation of insulin signaling preserves memory in animal models and appears beneficial for patients.In contrast, the role of insulin-like growth factor 1 (IGF1) remains controversial. Our aim was todetermine the possible protective actions of IGF1 in a rat SAD model induced by intracerebroventricularinjection of streptozotocin (icv-STZ). To this end, we drove the expression of IGF1 using a recombinantadenoviral vector, RAd-IGF1.Method: We evaluated 3 animal groups: Sham, STZ and STZ+IGF1. STZ and STZ+IGF1 groups wereinjected with 3 mg/kg icv-STZ and, 7 days later, the STZ+IGF1 group received the icv-RAd-IGF1.During the last two weeks until the end of the study (day 24 post icv-STZ), we performed severalbehavioral tests. Additionally, we analyzed neuroblast cells, synaptic proteins and IGF1-signalingpathway proteins in the hippocampus.Result: IGF1 improved marble-burying behavior, hippocampus-dependent spatial memory, objectrecognition memory and decreased depression-like behavior, all features affected by STZ. Also, brainIGF1 overexpression restored neurogenesis, enhanced SYT2, PSD95 and GAD65/67 levels, andmodulated the IGF1 receptor signaling pathway in STZ animals.Conclusion: Results indicate a protective role of IGF1 in our SAD model, as it was effective againstbehavior deficits and ameliorated hippocampal protein alterations induced by STZ. We conclude thatIGF1 therapy has an interesting potential for SAD treatment.