Hippocampal BDNF encapsulated cell bio‐delivery improves spontaneous behavioral alternations in the Y‐maze test in <i>App^NL‐G‐F</i> mice.

Background Alzheimer’s disease (AD) is an age-related characterized by synaptic dysfunction, brain inflammation, and neurodegeneration against which there no effective cure available. Brain-Derived Neurotrophic Factor (BDNF) a key molecule involved in the learning memory process, with crucial role plasticity neuronal survival. Several findings support that reduced BDNF expression human associated AD pathogenesis. has been proposed as potential therapy for AD, but low permeability. In this study, we used innovative encapsulated cell biodelivery (ECB) device containing cells capable of locally delivering to characterize its neuroprotective effects novel APP-knock-in mouse model AppNL-G-F. Method ECB devices ARPE-19 modified release were surgically bilaterally implanted hippocampus 3-month-old AppNL-G-F mice. on pathology evaluated after 1, 2, 3 months treatment immunohistochemical biochemical analysis. 3-month-treated groups, exploratory performances also using Elevated Plus Maze (EPM) Y-maze tests. Result The implants well tolerated signs unwanted side or weight loss. A high staining was detected most brains area surrounding at 1-3 months, retrieved showed variability release. Interestingly, three significantly improved mice´s anxiety behavior EPM spontaneous behavioral alternations test. Conclusion results study are encouraging promising approach treating cognitive decline. Optimization mouse-sized reduce needed future experiments translated larger clinical translation.