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

Abstract

AbstractBackgroundSporadic Alzheimer’s disease (SAD) is the most prevalent neurodegenerative disorder worldwide and it is characterized by progressive memory loss and cognitive impairment. Brain activation 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 to determine the possible protective actions of IGF1 in a rat SAD model induced by intracerebroventricular injection of streptozotocin (icv‐STZ). To this end, we drove the expression of IGF1 using a recombinant adenoviral vector, RAd‐IGF1.MethodWe evaluated 3 animal groups: Sham, STZ and STZ+IGF1. STZ and STZ+IGF1 groups were injected 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 several behavioral tests. Additionally, we analyzed neuroblast cells, synaptic proteins and IGF1‐signaling pathway proteins in the hippocampus.ResultIGF1 improved marble‐burying behavior, hippocampus‐dependent spatial memory, object recognition memory and decreased depression‐like behavior, all features affected by STZ. Also, brain IGF1 overexpression restored neurogenesis, enhanced SYT2, PSD95 and GAD65/67 levels, and modulated the IGF1 receptor signaling pathway in STZ animals.ConclusionResults indicate a protective role of IGF1 in our SAD model, as it was effective against behavior deficits and ameliorated hippocampal protein alterations induced by STZ. We conclude that IGF1 therapy has an interesting potential for SAD treatment.