INIBIOLP   05426
INSTITUTO DE INVESTIGACIONES BIOQUIMICAS DE LA PLATA "PROF. DR. RODOLFO R. BRENNER"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Neuroprotective Insulin-like Growth Factor 1 (IGF1) gene therapy for a rat model of sporadic Alzheimer's disease
Autor/es:
PARDO, J; LOPEZ HANOTTE, J; REGGIANI, PC; ZAPPA VILLAR, MF
Lugar:
Córdoba
Reunión:
Congreso; XXXIV Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias; 2019
Institución organizadora:
Sociedad Argentina de Investigación en Neurociencia (SAN)
Resumen:
Sporadic Alzheimer?s disease (SAD) is a progressive neurodegenerative disorder with no cure. We are interested in developing therapeutic strategies to overcome SAD-neurodegeneration. To this end, we implemented gene therapy (GT) for IGF1 in a rat SAD model induced by intracerebroventricular injection of streptozotocin (icv-STZ). Animals were divided into 3 experimental groups: Sham, STZ and STZ+IGF1. STZ and STZ+IGF1 groups received 3 mg/kg STZ-icv. Seven days later, the STZ+IGF1 group received icv an adenoviral vector expressing recombinant IGF1. During the last two weeks until the end of the study (day 24 post-icv-STZ), we performed several behavioral tests. Additionally, we performed in the hippocampus inmunohistochemistry to analyze neurogenesis and microglial cells, and Western Blots 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 decreased depression-like behavior, all features affected by STZ. Also, brain IGF1 overexpression restored neurogenesis in the STZ animals and modulated the microglial population. Importantly, the assessment of phosphorylated proteins levels revealed that IGF1 therapy effect was mediated by triggering IGF1 receptor signaling pathway. We conclude that IGF1 over-expression has an interesting potential for the treatment of SAD.