Therapeutic approach in an Alzheimer’s Disease rat model through GDNF overexpression by an astrocyte‐selective adeno‐associated virus

AAV-GDNF and AAV-GFP were generated, and the overexpression of transgenes was confirmed by RT-qPCR and IHC. In the therapeutic approach, animals belonging to STZ and GFP groups showed significant deterioration in all assessed behaviors. GDNF overexpression prevented cognitive impairment in treated animals, as they showed no significant differences compared to the SHAM group in the analysed parameters. Additionally, AAV-GDNF treatment promoted an increase in branching and length of processes in the analysed astrocytes CONCLUSION: We investigated an innovative therapeutic method specifically focused on hippocampal astrocytes. This allowed us to overexpress GDNF, generating protective actions that mitigated behavioral and cognitive alterations in our sAD animals. Furthermore, by acting on the brain's astrocyte population, promoting an increase in their complexity, we could potentially have a positive effect on maintaining cerebral homeostasis.