Impact of insulin-like Growth Factor 1 (IGF1) gene therapy on behaviour, neurogenesis, and synaptic proteins impairment in a non-transgenic rat model of Alzheimer's disease

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

Congreso; Federation of European Neuroscience Societies (FENS) 2020 Virtual Forum; 2020

Federation of European Neuroscience Societies (FENS)

Aims: Sporadic Alzheimer?s disease (SAD) is the most prevalent neurodegenerative disorder worldwide and it is characterized by progressive decline in memory and cognitive performance. Brain activation of insulin signalling 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), considering the fact that SAD has been recognized as an insulin resistant brain state. To this end, we drove the expression of IGF1 using a recombinant adenoviral vector, RAd-IGF1.Methods: We evaluated 3 animal groups: Sham, STZ and STZ+IGF1. STZ and STZ+IGF1 groups were injected with 3 mg/kg icv-STZ and, seven 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 behavioural tests. Additionally, we analysed neuroblast cells, synaptic proteins and IGF1-signaling pathway proteins in the hippocampus. Results: IGF1 improved marble-burying behaviour, hippocampus-dependent spatial memory, object recognition memory and decreased depression-like behaviour, all features affected by STZ. Also, brain IGF1 overexpression restored neurogenesis, enhanced SYT2, PSD95 and GAD65/67 levels, and modulated the IGF1 receptor signalling pathway in STZ animals. Conclusions: Results indicate a protective role of IGF1 in our SAD model, as it was effective against behaviour deficits and ameliorated hippocampal protein alterations induced by STZ. We conclude that IGF1 therapy has an interesting potential for SAD treatment.