Boosting Hippocampal Neurogenesis Rescues Cognitive Impairments in 3xTgAD Mouse Model of Alzheimer’s Disease

Abstract Background Alzheimer’s disease (AD) is an irreversible neurodegenerative disease with no treatment to date. Symptoms of AD include emotional disorders and memory impairments mainly resulting from dysfunction of the hippocampus, a brain area involved in learning, memory, navigation and regulation of mood. To attempt a rescue of hippocampal function in the disease, hippocampal neurogenesis was boosted in the Alzheimer’s mouse model. Method 3xTgAD mice were injected with lentiviruses encoding for Cdk4/cyclinD1 (lenti‐4D) as a means developed by our group to enhance neurogenesis in the dentate gyrus. 3xTgAD mice with increased levels of adult‐born granule cells were then examined for behavioral and cognitive performance. Result The genetic manipulation by lenti‐4D system increased the number of neural stem cells and adult hippocampal neurogenesis (two‐fold) in dentate gyrus of 10‐month‐old 3xTgAD mice. The increased neurogenesis rescued some of the behavioral effects observed in 3xTgAD mice. In the open‐field test, the mice with new‐born neurons showed decrease of behavioural inhibition. In the Morris water maze, the same group of mice performed less anxiety behaviours and more perseverance, which indicates better memory. Conclusion Increased neurogenesis by lenti‐4D system rescued some cognitive impairments in 3xTgAD mouse model of Alzheimer’s disease.